Gene(s) annotations

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GET /lookup/gene/TP53/hg19?add-all-data=1&format=api
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Content-Type: application/json
ETag: "c208801ecb765ef4571f83f290057c1a"
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{
    "symbol": "TP53",
    "gene_id": 33956,
    "description": "tumor protein p53",
    "synonyms": [
        "LFS1",
        "p53"
    ],
    "dgi": {
        "version": "sep_2016",
        "items": [
            {
                "drug_name_primary": "EP-2101",
                "drug_name_development": "EP-2101",
                "drug_name_trade": null,
                "drug_type": "Multiepitope DNA vaccine, emulsified in montanide ISA-51",
                "drug_class": "Vaccines",
                "drug_manufacturer": null,
                "drug_pubchem_cid": null,
                "drug_pubchem_sid": null,
                "disease": null,
                "gene_symbol": "TP53",
                "gene_category": null,
                "gene_entrez": "7157",
                "interaction_type": "Vaccine",
                "interaction_notes": null,
                "clinical_trial_id": null,
                "clinical_trial_details": null,
                "drug_approved": null
            },
            {
                "drug_name_primary": "Kevetrin",
                "drug_name_development": "granisetron",
                "drug_name_trade": null,
                "drug_type": null,
                "drug_class": null,
                "drug_manufacturer": null,
                "drug_pubchem_cid": "5284566",
                "drug_pubchem_sid": null,
                "disease": null,
                "gene_symbol": "P53",
                "gene_category": null,
                "gene_entrez": "7157",
                "interaction_type": "Activator",
                "interaction_notes": "p53 activator",
                "clinical_trial_id": "NCT01664000",
                "clinical_trial_details": "Advanced solid tumors A Phase 1, Open-Label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Kevetrin (Thioureidobutyronitrile) Administered Intravenously, in Patients With Advanced Solid Tumors",
                "drug_approved": null
            },
            {
                "drug_name_primary": "Kevetrin",
                "drug_name_development": null,
                "drug_name_trade": null,
                "drug_type": null,
                "drug_class": null,
                "drug_manufacturer": null,
                "drug_pubchem_cid": null,
                "drug_pubchem_sid": null,
                "disease": "Bladder Cancer",
                "gene_symbol": "TP53",
                "gene_category": "TSC1",
                "gene_entrez": null,
                "interaction_type": "Activator",
                "interaction_notes": null,
                "clinical_trial_id": "NCT01664000",
                "clinical_trial_details": "Purpose: Kevetrin activates p53",
                "drug_approved": null
            },
            {
                "drug_name_primary": "SGT-53",
                "drug_name_development": null,
                "drug_name_trade": null,
                "drug_type": null,
                "drug_class": null,
                "drug_manufacturer": null,
                "drug_pubchem_cid": null,
                "drug_pubchem_sid": null,
                "disease": "Bladder Cancer",
                "gene_symbol": "TP53",
                "gene_category": "TSC1",
                "gene_entrez": null,
                "interaction_type": "Activator",
                "interaction_notes": null,
                "clinical_trial_id": "NCT00470613",
                "clinical_trial_details": "Detailed description: SGT-53 is a complex composed of a wild type p53 gene",
                "drug_approved": null
            },
            {
                "drug_name_primary": "Mutant P53 Peptide Pulsed Dendritic Cell",
                "drug_name_development": null,
                "drug_name_trade": null,
                "drug_type": "Autologous dendritic cells pulsed with a mutant p53 peptide",
                "drug_class": "Vaccines",
                "drug_manufacturer": null,
                "drug_pubchem_cid": null,
                "drug_pubchem_sid": null,
                "disease": null,
                "gene_symbol": "TP53",
                "gene_category": null,
                "gene_entrez": "7157",
                "interaction_type": "Vaccine",
                "interaction_notes": null,
                "clinical_trial_id": null,
                "clinical_trial_details": null,
                "drug_approved": null
            },
            {
                "drug_name_primary": "Ad.P53-DC",
                "drug_name_development": "INGN-225",
                "drug_name_trade": null,
                "drug_type": "Autologous dendritic cells transduced with a recombinant adenovirus encoding p53 peptide",
                "drug_class": "Vaccines",
                "drug_manufacturer": null,
                "drug_pubchem_cid": null,
                "drug_pubchem_sid": null,
                "disease": null,
                "gene_symbol": "TP53",
                "gene_category": null,
                "gene_entrez": "7157",
                "interaction_type": "Vaccine",
                "interaction_notes": null,
                "clinical_trial_id": null,
                "clinical_trial_details": null,
                "drug_approved": null
            }
        ]
    },
    "cgd": {
        "version": "mar_2019",
        "pub_med_references": [
            1349175,
            1565143,
            1565144,
            1591732,
            1679237,
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            21946351,
            21990040,
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            22939227,
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            23409989,
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            23894400,
            30146126
        ],
        "condition": "Li-Fraumeni syndrome; Choroid plexus papilloma; Ependymoma, intracranial; Osteogenic sarcoma; Breast cancer, familial; Hepatoblastoma; Non-Hodgkin lymphoma; Adrenocortical carcinoma; Colorectal cancer; Bone marrow failure syndrome 5",
        "inheritance": "AD",
        "age_group": "Pediatric",
        "intervention_categories": [
            "Oncologic"
        ],
        "comments": "Variants may also be involved in susceptibility to a number of types of neoplasms (eg, Basal cell carcinoma, susceptibility to, Glioma, susceptibility to)",
        "intervention": null
    },
    "civic": {
        "version": "may_2019",
        "items": [
            {
                "variant": "DELETERIOUS MUTATION",
                "variant_summary": "Deleterious mutations are mutations of TP53 with prior characterization demonstrating significant deleterious effect on TP53 protein function. Inactivating TP53 mutations prevent on target activity and efficacy of MDM2-TP53 interaction inhibitors.",
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/221",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    22090360
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In a study of 74 patients with head and neck squamous cell carcinoma, those with disruptive mutations in TP53 had shorter overall survival and a higher rate of locoregional recurrence than those without mutations or with nondisruptive mutations.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/517",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Head And Neck Squamous Cell Carcinoma",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "5520"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    8901856
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "Unlike other studies, in this study of 110 patients with head and neck squamous cell carcinoma, there was no significant difference in the overall survival of patients with and without any TP53 mutations.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Does Not Support",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/518",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Head And Neck Squamous Cell Carcinoma",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "5520"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    19941080
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In a retrospective study of patients with esophageal carcinoma, those with mutations in TP53 had worse overall survival.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/519",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Esophagus Squamous Cell Carcinoma",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "3748"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    22699455
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In children with bone marrow relapsed B-cell precursor acute lymphoblastic leukemia, in multivariate analysis those with mutations in TP53 had worse event-free survival than patients without mutations.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/520",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Precursor B Lymphoblastic Lymphoma/leukemia",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "7061"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    24836762
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In patients with myelodysplastic syndrome, in a multivariate analysis those with mutations in TP53 had shorter overall survival than wild-type patients.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/521",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Myelodysplastic Syndrome",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "0050908"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    17215851
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In patients with myeloma, those with mutations in TP53 had worse overall survival than those without.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/522",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Myeloma",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "0070004"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    11325447
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "Tumors from 114 patients with head and neck squamous cell carcinoma were analyzed for TP53 mutations, 21 of which were treated with surgery. Unlike those treated with radiotherapy, those treated with surgery did not show a significant difference in rates of loco-regional control between those with and without mutations in TP53.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Does Not Support",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/523",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Head And Neck Squamous Cell Carcinoma",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "5520"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    11325447
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "Tumors from 114 patients with head and neck squamous cell carcinoma were analyzed for TP53 mutations. Of the 93 patients treated with radiotherapy, patients with mutations in TP53 had lower rates of loco-regional control and shorter disease-free, disease-specific, and overall survival.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/524",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Head And Neck Squamous Cell Carcinoma",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "5520"
            },
            {
                "variant": "TRUNCATING MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/223",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    21467160
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In patients with head and neck squamous cell carcinoma, in a multivariate analysis those with truncating mutations in TP53 had worse progression-free and overall survival than wild-type patients.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/525",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Head And Neck Squamous Cell Carcinoma",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "5520"
            },
            {
                "variant": "TRUNCATING MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/223",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    21467160
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In patients with head and neck squamous cell carcinoma, when comparing patients with any mutation in TP53 to wild-type, there was not a significant difference in overall survival in a multivariate analysis.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Does Not Support",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/526",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Head And Neck Squamous Cell Carcinoma",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "5520"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    21747090
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In relapsed B-ALL patients, TP53 mutations were associated with morphologic nonresponse to therapy (>5% blasts in the bone marrow after 9 weeks of treatment) as well as reduced event free and overall survival when compared to TP53 wildtype patients.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/640",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Precursor B Lymphoblastic Lymphoma/leukemia",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "7061"
            },
            {
                "variant": "DNA BINDING DOMAIN MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/242",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    12509970
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "Oral squamous cell carcinoma patients with TP53 mutations in the DNA binding domain (L2, L3 and the LSH motif) have significantly reduced cumulative survival when compared to patients with TP53 mutations outside of this DNA binding domain. These mutations were also significantly associated with locoregional failure, cervical lymph node metastasis and distant metastasis, likely contributing to this finding.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/641",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Oral Squamous Cell Carcinoma",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "0050866"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    24740294
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "B",
                "evidence_statement": "In this meta-analysis of 13 studies (564 patients) p53 positivity as defined by high protein expression and/or p53 mutation was associated with improved response to chemotherapy (risk ratio [RR] = 0.704; 95% confidence intervals [CI] = 0.550-0.903; P = 0.006).",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/850",
                "drugs": [
                    "Chemotherapy"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Gastric Adenocarcinoma",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "3717"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    22698404
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "D",
                "evidence_statement": "In this preclinical study, MMTV-Wnt1 mammary tumors with mutant TP53 showed a better clinical response to chemotherapy (doxorubicin) than TP53 wild-type tumors. This was mediated by wild-type TP53-induced cell-arrest under chemotherapy even in the context of heterozygous TP53 point mutations or absence of p21. Thus the status of both TP53 alleles should be assessed because even one copy of wild-type TP53 may contribute to poor response to chemotherapy.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/851",
                "drugs": [
                    "Doxorubicin"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Breast Cancer",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1612"
            },
            {
                "variant": "WILD TYPE",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/369",
                "variant_origin": null,
                "pub_med_references": [
                    24957073
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "B",
                "evidence_statement": "In this retrospective biomarker analysis of the EXPERT-C trial, patients with TP53 wild-type status had a statistically significant better progression free survival (PFS) (89.3% vs 65.0% at 5 years; hazard ratio [HR] = 0.23; 95% confidence interval [CI] = 0.07 to 0.78; two-sided P = .02 by Cox regression) and overall survival (OS) (92.7% vs 67.5% at 5 years; HR = 0.16; 95% CI = 0.04 to 0.70; two-sided P = .02 by Cox regression) when treated with Cetuximab + CAPOX (Capecitabine, Oxaliplatin) than in the control arm without Cetuximab.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/875",
                "drugs": [
                    "Cetuximab",
                    "Capecitabine",
                    "Oxaliplatin"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Colorectal Cancer",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "9256"
            },
            {
                "variant": "WILD TYPE",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/369",
                "variant_origin": null,
                "pub_med_references": [
                    23515910
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "B",
                "evidence_statement": "Patients with p53 wild type (as defined by low expression and/or wild-type tp53 gene) had a higher response rate to chemotherapy-based treatment (total major response [MR]: risk ratio [RR] = 1.09, 95 % CI = 1.03-1.16, P = .003; pathological MR: RR = 1.15, 95 % CI = 1.06-1.25, P = .001; total complete response [CR]: RR = 1.08, 95 % CI = 1.00-1.17, P = .040) in this meta-analysis (28 studies, 1497 cases).",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/906",
                "drugs": [
                    "Chemotherapy"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Esophageal Carcinoma",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1107"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    26771088
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In a study of 97 patients with AML  treated with HSCT, 40 had TP53 mutations comprising a total of 44 mutations. Patients with a TP53 mutation had a reduced three year probability of overall survival and event-free survival compared to patients with the wild-type TP53.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1018",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Acute Myeloid Leukemia",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "9119"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    15922892
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "TP53 mutation was shown to be associated with shorter overall survival in patients with adrenocortical tumors (log-rank test; P=0.098). Of 20 patients studied, 5 had coding mutation in TP53. Four of the 5 patients with a TP53 mutation had metastases at diagnosis or detected soon thereafter, and 3 of 4 died of disease within 12 months of surgical resection.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1028",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Adrenocortical Carcinoma",
                "rating": "2",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "3948"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    22425996
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "D",
                "evidence_statement": "A clinical trial comparing selumetinib and docetaxel vs. docetaxel and placebo in KRAS mutant NSCLC was recapitulated in mice. Tumors were induced in lung epithelium by nasal instillation of CRE-bearing adenovirus in conditionally targeted mice. Kras(G12D) and Trp53 knockout mutant mice were resistant to docetaxel monotherapy but sensitive to combined treatment. In a small number of human NSCLC patients with these genotypes FDG-PET signal intensity changes and pERK IHC staining correlated with mouse data.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1145",
                "drugs": [
                    "Docetaxel",
                    "Selumetinib (AZD6244)"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Non-small Cell Lung Carcinoma",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "3908"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    22425996
                ],
                "clinical_significance": "Resistance",
                "evidence_level": "D",
                "evidence_statement": "A clinical trial comparing selumetinib and docetaxel vs. docetaxel and placebo in KRAS mutant NSCLC was recapitulated in mice. Tumors were induced in lung epithelium by nasal instillation of CRE-bearing adenovirus in conditionally targeted mice. Kras(G12D) and Trp53 knockout mutant mice were resistant to docetaxel monotherapy but sensitive to combined treatment. In a small number of human NSCLC patients with these genotypes FDG-PET signal intensity changes and pERK IHC staining correlated with mouse data.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1146",
                "drugs": [
                    "Docetaxel"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Non-small Cell Lung Carcinoma",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "3908"
            },
            {
                "variant": "DELETERIOUS MUTATION",
                "variant_summary": "Deleterious mutations are mutations of TP53 with prior characterization demonstrating significant deleterious effect on TP53 protein function. Inactivating TP53 mutations prevent on target activity and efficacy of MDM2-TP53 interaction inhibitors.",
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/221",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    26899019
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "Pooled analysis of TP53 mutations (exons 5-8) from 4 randomized trials (IALT, JBR10, CALGB-9633 and ANITA). Mutations (434; 36%) had no prognostic effect (OBS: HROS=0.99; [95%CI 0.77-1.28], p=0.95; HRDFS=0.99 [0.78-1.25], p=0.92) but were marginally predictive of benefit from ACT for OS (test for interaction: OS: p=0.06; DFS: p=0.11).",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Does Not Support",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1147",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Non-small Cell Lung Carcinoma",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "3908"
            },
            {
                "variant": "DELETERIOUS MUTATION",
                "variant_summary": "Deleterious mutations are mutations of TP53 with prior characterization demonstrating significant deleterious effect on TP53 protein function. Inactivating TP53 mutations prevent on target activity and efficacy of MDM2-TP53 interaction inhibitors.",
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/221",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    26899019
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "B",
                "evidence_statement": "Pooled analysis of TP53 mutations (exons 5-8) from 4 randomized trials (IALT, JBR10, CALGB-9633 and ANITA) of platinum-based adjuvant chemotherapy (ACT) versus observation (OBS). Patients with TP53wt had significantly better PFS and OS with ACT vs. OBS (p=0.005, p=0.02, respectively) whereas patients with TP53 mutations did not show significant differences in PFS and OS between ACT and OBS (p=0.86, p=0.63).",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Does Not Support",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1148",
                "drugs": [
                    "Adjuvant Chemotherapy"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Non-small Cell Lung Carcinoma",
                "rating": "2",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "3908"
            },
            {
                "variant": "WILD TYPE",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/369",
                "variant_origin": null,
                "pub_med_references": [
                    26899019
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "B",
                "evidence_statement": "Pooled analysis of TP53 mutations (exons 5-8) from 4 randomized trials (IALT, JBR10, CALGB-9633 and ANITA, 1209 patients, median follow-up 5.5 years) of platinum-based adjuvant chemotherapy (ACT) versus observation (OBS). Patients with wild-type TP53 had better outcomes with ACT than OBS (HROS=0.77 [0.62-0.95], p=0.02; HRDFS=0.75 [0.62-0.92], p=0.005).",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1149",
                "drugs": [
                    "Adjuvant Chemotherapy"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Non-small Cell Lung Carcinoma",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "3908"
            },
            {
                "variant": "DELETERIOUS MUTATION",
                "variant_summary": "Deleterious mutations are mutations of TP53 with prior characterization demonstrating significant deleterious effect on TP53 protein function. Inactivating TP53 mutations prevent on target activity and efficacy of MDM2-TP53 interaction inhibitors.",
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/221",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    26646755
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "B",
                "evidence_statement": "19 advanced sarcoma patients treated with pazopanib were retrospectively assessed for mutations associated with response using the Foundation one sarcoma/heme panel. Progression-free survival (PFS) of patients with TP53 mutations (all predicted to be loss of function) was significantly greater than TP53 wild-type tumors with the median PFS of 208 versus 136 days, respectively [P = 0.036, hazards ratio 0.38 (95% confidence interval 0.09-0.83)].",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1170",
                "drugs": [
                    "Pazopanib"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Sarcoma",
                "rating": "2",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1115"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    8241511
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "A study of 53 patients with B-CLL found a significant resistance to chemotherapy and corresponding poor clinical outcomes among the 7 treated patients with p53 mutations compared to the 29 treated patients without.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1450",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Chronic Lymphocytic Leukemia",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1040"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    18689542
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In a study of 126 patients with long-term follow-up, TP53 mutations were significantly associated with shorter median survival in patients (P = 0.002) from time of diagnosis. The median survival from the time of first observation of a TP53 mutation was much more pronounced (P = <0.001). These findings were statistically independent of 17p deletions.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1451",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Chronic Lymphocytic Leukemia",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1040"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    20697090
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "The authors analyzed 328 patients with CLL, of which 28 were identified to have TP53 mutations. Patients with TP53 mutations were found to have significantly shorter progression-free (HR = 3.8; P < 0.001) and overall survival (HR = 7.2; P < 0.001).",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1452",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Chronic Lymphocytic Leukemia",
                "rating": "5",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1040"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    21483000
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In the CLL4 trial assessing first line treatment with chlorambucil or fludarabine with or without cyclophosphamide, patients with TP53 mutations experienced poorer overall response rates (27% vs 83%), shorter progression free survival (5 year PFS 5% vs 17%), and overall survival (20% vs 59%) compared to patients without TP53 mutations.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1478",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Chronic Lymphocytic Leukemia",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1040"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    14726385
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "B",
                "evidence_statement": "Thirty-six patients with CLL were treated with alemtuzumab. Partial or complete response was achieved in 6 of 15 patients with p53 mutations, compared to 4 of 21 without. These findings are not statistically significant, but the authors suggest that alemtuzumab is an effective therapy for patients with p53 mutations or deletions.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1481",
                "drugs": [
                    "Alemtuzumab"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Chronic Lymphocytic Leukemia",
                "rating": "2",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1040"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    24943832
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "In a multivariate analysis of 774 CLL patients, TP53 aberrations were significantly correlated with shorter time to first treatment (HR=2.081; 95% CI=1.431-3.021). This finding was independent of IGHV mutation status.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1485",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Chronic Lymphocytic Leukemia",
                "rating": "5",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1040"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    26837699
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "A",
                "evidence_statement": "In a cohort of 406 patients with CLL, those patients with clonal or sub-clonal mutations in TP53 had significantly shorter overall survival (HR: 1.71; 95% CI: 1.28-2.26; P = .0001).",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/1507",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Chronic Lymphocytic Leukemia",
                "rating": "5",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1040"
            },
            {
                "variant": "OVEREXPRESSION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/1306",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    11595686
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "p53 overexpression (>10% positive stained nuclei) was found in 110 cases from a 178 patient cohort with invasive ovarian carcinoma who had undergone surgery. Overexpression of p53 was correlated with poor differentiation (p<0.001) and high S-phase fraction (p<0.001).",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2697",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Ovarian Cancer",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "2394"
            },
            {
                "variant": "DNA BINDING DOMAIN MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/242",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    10786679
                ],
                "clinical_significance": "Resistance",
                "evidence_level": "B",
                "evidence_statement": "In a study 202 breast cancer patients undergoing first line tamoxifen treatment, 65 patients had mutations in TP53. Among the p53 wild type population a 66% response rate was reported, where response was considered as complete response, partial response or stable disease. In a patient subgroup with mutations in p53 amino acids that directly interact with DNA, 2 of 11 (18%) of patients responded to tamoxifen.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2783",
                "drugs": [
                    "Tamoxifen"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Breast Cancer",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1612"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    10786679
                ],
                "clinical_significance": "Resistance",
                "evidence_level": "C",
                "evidence_statement": "In a study 202 breast cancer patients undergoing tamoxifen treatment, a higher frequency of wildtype TP53 patients responded to treatment compared to those with mutations in TP53 (66% wild-type vs. 31%, odds ratio (OR):0.22, 95CI:0.12-0.42, P<0.0001, univariate analysis; OR:0.29, 95% CI:0.12-0.42, P=0.0014, multivariate analysis). The median survival after start of therapy was shorter in patients with mutations in TP53 than for patients with wild-type TP53 (20mo vs. 29mo, HR:1.99,95% CI:1.43-2.75, P<0.001). Breast cancer patients with TP53 mutations also had a decrease in progression-free survival (HR:2.61, 95% CI:1.90-3.6, P<0.001).",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2784",
                "drugs": [
                    "Tamoxifen"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Breast Cancer",
                "rating": "1",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1612"
            },
            {
                "variant": "OVEREXPRESSION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/1306",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    14514923
                ],
                "clinical_significance": null,
                "evidence_level": "B",
                "evidence_statement": "In a Phase II trial of 25 patients with metastaic gastric cancer, patients received preoperative high dose chemotherapy (HDCT) consisting of etoposide, cisplatin and mitomycin. Patients with greater than 50% regression in response to HDCT received surgery. TP53 overexpression was assayed by immunohistochemistry. 14 patients showed p53 overexpression, and 12 of these qualified for resection. Overall survival in patients with p53 overexpression was 17.3 months in contrast to patients with negative p53 immunohistochemistry, where it was 7.2 months (p=0.0003).",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2799",
                "drugs": [
                    "Cisplatin",
                    "Mitomycin",
                    "Etoposide"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Stomach Cancer",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "10534"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    14514923
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "C",
                "evidence_statement": "In a study of 25 patients with advanced gastric cancer, mutations in TP53 were identified in 32% of primary tumors. TP53 mutations were associated with an improved response to preoperative treatment of a modified EAP protocol (combination of doxorubicin, etoposide and cisplatin). Patients with mutations in TP53 had an increased median survival compared to patients with wildtype TP53 (18.5mo vs. 10.2mo, P=0.044).",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2820",
                "drugs": [
                    "EAP Protocol"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Stomach Carcinoma",
                "rating": "1",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "5517"
            },
            {
                "variant": "WILD TYPE",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/369",
                "variant_origin": null,
                "pub_med_references": [
                    17671205
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "D",
                "evidence_statement": "MDM2 Inhibitor Nutlin-3a induced senescence in presence of functional TP53 in murine primary fibroblasts, oncogenically transformed fibroblasts, and fibrosarcoma cell lines. Cells lacking functional TP53 were completely insensitive to the drug.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2963",
                "drugs": [
                    "Nutlin-3a"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Cancer",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "162"
            },
            {
                "variant": "WILD TYPE",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/369",
                "variant_origin": null,
                "pub_med_references": [
                    25730903
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "D",
                "evidence_statement": "MDM2 Inhibitor screen in a panel of 260 cancer cell lines with well characterized TP53  status shows that only cancer cell lines with unaltered TP53 may be sensitive to MDM2 Inhibitor.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2964",
                "drugs": [
                    "AMGMDS3"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Cancer",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "162"
            },
            {
                "variant": "WILD TYPE",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/369",
                "variant_origin": null,
                "pub_med_references": [
                    26459177
                ],
                "clinical_significance": "Sensitivity/Response",
                "evidence_level": "B",
                "evidence_statement": "Phase I Trial of RG7112 in 116 heavily pretreated patients with AML, ALL, CML, CLL, sCLL demonstrated sustained clinical improvement and induction of TP53 target genes in subset of patients with wild type TP53. 96 patients were tested for TP53 mutation and 19 cases of mutation were detected. No sustained clinical improvement or induction of TP53 target genes was observed in patients with mutant TP53.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2965",
                "drugs": [
                    "RG7112"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Leukemia",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1240"
            },
            {
                "variant": "DELETERIOUS MUTATION",
                "variant_summary": "Deleterious mutations are mutations of TP53 with prior characterization demonstrating significant deleterious effect on TP53 protein function. Inactivating TP53 mutations prevent on target activity and efficacy of MDM2-TP53 interaction inhibitors.",
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/221",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    26459177
                ],
                "clinical_significance": "Resistance",
                "evidence_level": "B",
                "evidence_statement": "Phase I Trial of MDM2 inhibitor RG7112 in 116 patients with AML, ALL, CML, CLL, sCLL demonstrated sustained clinical improvement and induction of TP53 target genes in subset of patients with wild type TP53. No sustained clinical improvement or induction of TP53 target genes was observed in patients with mutant TP53.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2966",
                "drugs": [
                    "RG7112"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Leukemia",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "1240"
            },
            {
                "variant": "DELETERIOUS MUTATION",
                "variant_summary": "Deleterious mutations are mutations of TP53 with prior characterization demonstrating significant deleterious effect on TP53 protein function. Inactivating TP53 mutations prevent on target activity and efficacy of MDM2-TP53 interaction inhibitors.",
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/221",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    25730903
                ],
                "clinical_significance": "Resistance",
                "evidence_level": "D",
                "evidence_statement": "MDM2 Inhibitor screen in a panel of 260 cancer cell lines with well characterized TP53 status shows that only cancer cell lines with unaltered TP53 may be sensitive to MDM2 Inhibitor AMGMDS3, while those with p53 mutations demonstrated resistance.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2967",
                "drugs": [
                    "AMGMDS3"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Cancer",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "162"
            },
            {
                "variant": "DELETERIOUS MUTATION",
                "variant_summary": "Deleterious mutations are mutations of TP53 with prior characterization demonstrating significant deleterious effect on TP53 protein function. Inactivating TP53 mutations prevent on target activity and efficacy of MDM2-TP53 interaction inhibitors.",
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/221",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    17671205
                ],
                "clinical_significance": "Resistance",
                "evidence_level": "D",
                "evidence_statement": "MDM2 Inhibitor Nutlin-3a induced senescence in presence of functional TP53 in murine primary fibroblasts, oncogenically transformed fibroblasts, and fibrosarcoma cell lines. TP53 mutant cells lacking functional TP53 were completely insensitive to the drug.",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2968",
                "drugs": [
                    "Nutlin-3a"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Cancer",
                "rating": "4",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "162"
            },
            {
                "variant": "CONSERVED DOMAIN MUT",
                "variant_summary": "This conserved domain mutation variant covers mutations in regions of p53 reported to be highly conserved during evolution. These regions span codons 117-143 (region II), 171-181 (region III), 234-258 (region (IV), and 270-286 (region V). Region I covers approximately codons 10 through 25 but does not appear in all studies on conserved domain mutations. There is overlap with these regions and reported regions of hotspot p53 mutations, where it is observed that hotspots for detrimental mutation correspond to more highly evolutionary conserved regions. While there is agreement and overlap between different reports, the literature does not seem to indicate an exact consensus on these regions of human p53 at this time, but the four highly conserved regions are part of the DNA binding domain, and are reported to exist within codons 97 to 292.",
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/1300",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    11595686
                ],
                "clinical_significance": "Poor Outcome",
                "evidence_level": "B",
                "evidence_statement": "Patients with conserved domain p53 mutation (n=61) were compared with those with wild type or non-conserved domain p53 mutation (n=117) in a cohort of 178 invasive ovarian carcinoma patients who had undergone surgery. Overall survival was decreased in the cohort with conserved domian mutation (p=0.005).  Conserved domain mutation was an independent factor in univariate (but not multivariate) analysis of overall survival with relative risk 1.70 (1.17-2.47, p<0.007).",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2993",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Ovarian Cancer",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "2394"
            },
            {
                "variant": "MUTATION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/222",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    28453411
                ],
                "clinical_significance": null,
                "evidence_level": "B",
                "evidence_statement": "A pooled analysis to investigate the prognostic and predictive roles of TP53/KRAS and TP53/EGFR comutations (cm) in randomized trials of adjuvant chemotherapy compared to observational therapy encompassing a total of 3,553 patients. TP53/KRAS cm showed no prognostic effects but a borderline predictive effect (p=0,04) for negative effect of chemotherapy as compared to tp53/KRAS wt/wt. TP53/EGFR cm in was neither prognostic ( P = .83), nor significantly predictive ( P = .86). Similar results were observed for both groups for disease-free survival.",
                "evidence_type": "Prognostic",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/2999",
                "drugs": null,
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Non-small Cell Lung Carcinoma",
                "rating": "5",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "3908"
            },
            {
                "variant": "OVEREXPRESSION",
                "variant_summary": null,
                "variant_civic_url": "https://civic.genome.wustl.edu/links/variants/1306",
                "variant_origin": "Somatic Mutation",
                "pub_med_references": [
                    11595686
                ],
                "clinical_significance": "Resistance",
                "evidence_level": "B",
                "evidence_statement": "In a study involving patients with invasive ovarian carcinoma who had undergone surgery, a subset of 73 patients were classified via response to platinum-based chemotherapy as sensitive or resistant/refractory and tested for p53 overexpression (>10% postive stained nuclei). 78% of p53 negative patients were classified as sensitive, in compariston to 39% of p53 positive patients (p=0.001).",
                "evidence_type": "Predictive",
                "evidence_status": "accepted",
                "evidence_direction": "Supports",
                "evidence_civic_url": "https://civic.genome.wustl.edu/links/evidence_items/3013",
                "drugs": [
                    "Cisplatin",
                    "Carboplatin"
                ],
                "transcripts": null,
                "representative_transcript": "ENST00000269305.4",
                "disease": "Ovarian Cancer",
                "rating": "3",
                "gene": "TP53",
                "gene_civic_url": "https://civic.genome.wustl.edu/links/genes/45",
                "entrez_id": "7157",
                "doid": "2394"
            }
        ]
    },
    "dbnsfp_genes": {
        "version": "v3_4",
        "items": [
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                "kegg": {
                    "id": [
                        "hsa04010",
                        "hsa04110",
                        "hsa04115",
                        "hsa04210",
                        "hsa04310",
                        "hsa05030",
                        "hsa05040",
                        "hsa05210",
                        "hsa05212",
                        "hsa05213",
                        "hsa05214",
                        "hsa05215",
                        "hsa05216",
                        "hsa05217",
                        "hsa05218",
                        "hsa05219",
                        "hsa05220",
                        "hsa05222",
                        "hsa05223"
                    ],
                    "full": [
                        "MAPK signaling pathway",
                        "Cell cycle",
                        "p53 signaling pathway",
                        "Apoptosis",
                        "Wnt signaling pathway",
                        "Amyotrophic lateral sclerosis (ALS)",
                        "Huntington's disease",
                        "Colorectal cancer",
                        "Pancreatic cancer",
                        "Endometrial cancer",
                        "Glioma",
                        "Prostate cancer",
                        "Thyroid cancer",
                        "Basal cell carcinoma",
                        "Melanoma",
                        "Bladder cancer",
                        "Chronic myeloid leukemia",
                        "Small cell lung cancer",
                        "Non-small cell lung cancer"
                    ]
                },
                "expressions_rpkm": {
                    "skin___not_sun_exposed__suprapubic": 20.111400000000003,
                    "heart___atrial_appendage": 4.47295,
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                    "esophagus___muscularis": 7.1133999999999995,
                    "brain___putamen__basal_ganglia": 2.84816,
                    "muscle___skeletal": 3.88969,
                    "vagina": 12.7549,
                    "small_intestine___terminal_ileum": 11.6496,
                    "cells___ebv_transformed_lymphocytes": 38.38779999999999,
                    "brain___spinal_cord__cervicalc_1": 2.49533,
                    "adipose___visceral__omentum": 9.99357,
                    "esophagus___mucosa": 14.6588,
                    "colon___sigmoid": 7.76274,
                    "heart___left_ventricle": 3.58802,
                    "liver": 5.52354,
                    "skin___sun_exposed__lower_leg": 20.445199999999996,
                    "brain___frontal_cortex__ba9": 2.2682300000000004,
                    "cervix___endocervix": 13.458,
                    "colon___transverse": 11.9071,
                    "breast___mammary_tissue": 14.0185,
                    "artery___aorta": 8.69709,
                    "fallopian_tube": 14.1707,
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                    "brain___substantia_nigra": 3.05483,
                    "brain___cerebellar_hemisphere": 1.04868,
                    "minor_salivary_gland": 11.3432,
                    "brain___hippocampus": 2.2206300000000003,
                    "brain___nucleus_accumbens__basal_ganglia": 2.73408,
                    "adipose___subcutaneous": 12.0517,
                    "kidney___cortex": 7.37007,
                    "artery___coronary": 9.187259999999998,
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                    "brain___hypothalamus": 2.5338399999999996,
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                    "artery___tibial": 9.10642,
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                    "lung": 9.20619,
                    "esophagus___gastroesophageal_junction": 7.78288,
                    "brain___caudate__basal_ganglia": 3.26298,
                    "pancreas": 6.3052600000000005,
                    "cervix___ectocervix": 13.9891,
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                    "brain___cortex": 2.6111999999999997,
                    "whole_blood": 6.00388,
                    "adrenal_gland": 9.03215,
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                    "bladder": 14.246299999999998,
                    "brain___amygdala": 3.10035,
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                    "cells___transformed_fibroblasts": 14.0786
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                "gene_symbol": "TP53"
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    },
    "exac_genes": {
        "version": "sep_2018",
        "items": [
            {
                "prec": 0.08775030000000002,
                "pnull": 2.67186e-05,
                "pli": 0.912223,
                "syn_z": -0.042240200000000006,
                "mis_z": 1.37892,
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                "segdups": 0,
                "flag": false
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        ]
    },
    "pub_med_articles": {
        "": {
            "abstract": "To characterize cancer risk in heterozygous p53 mutation carriers, we analyzed cancer incidence in 56 germline p53 mutation carriers and 3,201 noncarriers from 107 kindreds ascertained through patients with childhood soft-tissue sarcoma who were treated at the University of Texas M. D. Anderson Cancer Center. We systematically followed members in these kindreds for cancer incidence for >20 years and evaluated their p53 gene status. We found seven kindreds with germline p53 mutations that include both missense and truncation mutation types. Kaplan-Meier analysis showed similar cancer risks between 21 missense and 35 truncation p53 mutation carriers (log-rank chi(2)=0.04; P=.84). We found a significantly higher cancer risk in female carriers than in male carriers (log-rank chi(2)=12.1; P<.001), a difference not explained by an excess of sex-specific cancer. The calculated standardized incidence ratio (SIR) showed that mutation carriers had a risk for all types of cancer that was much higher than that for the general population (SIR = 41.1; 95% confidence interval [CI] 29.9-55.0) whereas noncarriers had a risk for all types of cancer that was similar to that in the general population (SIR = 0.9; 95% CI 0.8-1.0). The calculated SIRs showed a >100-fold higher risk of sarcoma, female breast cancer, and hematologic malignancies for the p53 mutation carriers and agreed with the findings of an earlier segregation analysis based on the same cohort. These results quantitatively illustrated the spectrum of cancer risk in germline p53 mutation carriers and will provide valuable reference for the evaluation and treatment of patients with cancer.",
            "journal_issue": "volume:72, issue:4",
            "date_completed": 20030505,
            "date_published": 20030400,
            "journal": "American journal of human genetics",
            "title": "Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk.",
            "pub_med_id": 12610779,
            "authors": [
                "Hwang, SJ",
                "Lozano, G",
                "Amos, CI",
                "Strong, LC"
            ],
            "journal_abbreviation": "Am. J. Hum. Genet.",
            "format": "Article"
        }
    },
    "identifiers": {
        "hgnc_previous_symbol": null,
        "hgnc_id": null,
        "uniprot_id": [
            "A0A087WT22",
            "A0A087WXZ1",
            "A0A087WZU8",
            "A0A087X1Q1",
            "A0A0U1RQC9",
            "E7EMR6",
            "E7EQX7",
            "E7ESS1",
            "E9PCY9",
            "E9PFT5",
            "I3L0W9",
            "J3KP33",
            "P04637",
            "S4R334"
        ],
        "ensembl_id": null,
        "entrez_id": [
            "7157"
        ],
        "lrg_id": [
            "LRG_321"
        ]
    },
    "ghr_genes": {
        "version": "apr_2019",
        "items": [
            {
                "html_text": "<p>The <i>TP53</i> gene provides instructions for making a protein called tumor protein p53 (or p53). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way.</p><p>The p53 protein is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the damaged cell will self-destruct (undergo apoptosis). If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors.</p><p>Because p53 is essential for regulating cell division and preventing tumor formation, it has been nicknamed the \"guardian of the genome.\"</p>",
                "date_published_by_ghr": "2019-04-02",
                "conditions_list": [
                    {
                        "name": "Bladder Cancer",
                        "html_text": "<p>Bladder cancer is a disease in which certain cells in the bladder become abnormal and multiply without control or order.  The bladder is a hollow, muscular organ in the lower abdomen that stores urine until it is ready to be excreted from the body. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called transitional cell carcinoma (TCC).</p><p>Bladder cancer may cause blood in the urine, pain during urination, frequent urination, or the feeling that one needs to urinate without results. These signs and symptoms are not specific to bladder cancer, however. They also can be caused by noncancerous conditions such as infections.</p>",
                        "ghr_link": "https://ghr.nlm.nih.gov/condition/bladder-cancer"
                    },
                    {
                        "name": "Breast Cancer",
                        "html_text": "<p>Breast cancer is a disease in which certain cells in the breast become abnormal and multiply uncontrollably to form a tumor. Although breast cancer is much more common in women, this form of cancer can also develop in men.  In both women and men, the most common form of breast cancer begins in cells lining the milk ducts (ductal cancer). In women, cancer can also develop in the glands that produce milk (lobular cancer). Most men have little or no lobular tissue, so lobular cancer in men is very rare.</p><p>In its early stages, breast cancer usually does not cause pain and may exhibit no noticeable symptoms. As the cancer progresses, signs and symptoms can include a lump or thickening in or near the breast; a change in the size or shape of the breast; nipple discharge, tenderness, or retraction (turning inward); and skin irritation, dimpling, or scaliness. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a person definitely has breast cancer.</p><p>In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If breast cancer spreads, cancerous cells most often appear in the bones, liver, lungs, or brain. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.</p><p>A small percentage of all breast cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary breast cancers tend to develop earlier in life than noninherited (sporadic) cases, and new (primary) tumors are more likely to develop in both breasts.</p>",
                        "ghr_link": "https://ghr.nlm.nih.gov/condition/breast-cancer"
                    },
                    {
                        "name": "Cholangiocarcinoma",
                        "html_text": "<p>Cholangiocarcinoma is a group of cancers that begin in the bile ducts. Bile ducts are branched tubes that connect the liver and gallbladder to the small intestine. They carry bile, which is a fluid that helps the body digest the fats in food. Bile is produced in the liver and stored in the gallbladder before being released in the small intestine after a person eats.</p><p>Cholangiocarcinoma is classified by its location in relation to the liver. Intrahepatic cholangiocarcinoma begins in the small bile ducts within the liver. This is the least common form of the disease, accounting for less than 10 percent of all cases. Perihilar cholangiocarcinoma (also known as a Klatskin tumor) begins in an area called the hilum, where two major bile ducts join and leave the liver. It is the most common form of the disease, accounting for more than half of all cases. The remaining cases are classified as distal cholangiocarcinomas, which begin in bile ducts outside the liver. The perihilar and distal forms of the disease, which both occur outside the liver, are sometimes grouped together and called extrahepatic cholangiocarcinoma.</p><p>The three types of cholangiocarcinoma do not usually cause any symptoms in their early stages, and this cancer is usually not diagnosed until it has already spread beyond the bile ducts to other tissues. Symptoms often result when bile ducts become blocked by the tumor. The most common symptom is jaundice, which is a yellowing of the skin and the whites of the eyes. Other symptoms can include itching, dark-colored urine, loss of appetite, unintentional weight loss, abdominal pain, and light-colored and greasy stools. These symptoms are described as \"nonspecific\" because they can be features of many different diseases.</p><p>Most people who develop cholangiocarcinoma are older than 65. Because this cancer is often not discovered until it has already spread, it can be challenging to treat effectively. Affected individuals can survive for several months to several years after diagnosis.</p>",
                        "ghr_link": "https://ghr.nlm.nih.gov/condition/cholangiocarcinoma"
                    },
                    {
                        "name": "Head And Neck Squamous Cell Carcinoma",
                        "html_text": "<p>Squamous cell carcinoma is a cancer that arises from particular cells called squamous cells. Squamous cells are found in the outer layer of skin and in the mucous membranes, which are the moist tissues that line body cavities such as the airways and intestines. Head and neck squamous cell carcinoma (HNSCC) develops in the mucous membranes of the mouth, nose, and throat.</p><p>HNSCC is classified by its location: it can occur in the mouth (oral cavity), the middle part of the throat near the mouth (oropharynx), the space behind the nose (nasal cavity and paranasal sinuses), the upper part of the throat near the nasal cavity (nasopharynx), the voicebox (larynx), or the lower part of the throat near the larynx (hypopharynx). Depending on the location, the cancer can cause abnormal patches or open sores (ulcers) in the mouth and throat, unusual bleeding or pain in the mouth, sinus congestion that does not clear, sore throat, earache, pain when swallowing or difficulty swallowing, a hoarse voice, difficulty breathing, or enlarged lymph nodes.</p><p>HNSCC can spread (metastasize) to other parts of the body, such as the lymph nodes or lungs. If it spreads, the cancer has a worse prognosis and can be fatal. About half of affected individuals survive more than five years after diagnosis.</p>",
                        "ghr_link": "https://ghr.nlm.nih.gov/condition/head-and-neck-squamous-cell-carcinoma"
                    },
                    {
                        "name": "Li-Fraumeni Syndrome",
                        "html_text": "<p>Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults.</p><p>The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called soft tissue sarcomas.  Other cancers commonly seen in this syndrome include brain tumors, cancers of blood-forming tissues (leukemias), and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney).  Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome.</p><p>A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome.  Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different.</p>",
                        "ghr_link": "https://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome"
                    },
                    {
                        "name": "Lung Cancer",
                        "html_text": "<p>Lung cancer is a disease in which certain cells in the lungs become abnormal and multiply uncontrollably to form a tumor. Lung cancer may not cause signs or symptoms in its early stages. Some people with lung cancer have chest pain, frequent coughing, blood in the mucus, breathing problems, trouble swallowing or speaking, loss of appetite and weight loss, fatigue, or swelling in the face or neck. Additional symptoms can develop if the cancer spreads (metastasizes) into other tissues. Lung cancer occurs most often in adults in their sixties or seventies. Most people who develop lung cancer have a history of long-term tobacco smoking; however, the condition can occur in people who have never smoked.</p><p>Lung cancer is generally divided into two types, small cell lung cancer and non-small cell lung cancer, based on the size of the affected cells when viewed under a microscope. Non-small cell lung cancer accounts for 85 percent of lung cancer, while small cell lung cancer accounts for the remaining 15 percent.</p><p>Small cell lung cancer grows quickly and in more than half of cases the cancer has spread beyond the lung by the time the condition is diagnosed. Small cell lung cancer often metastasizes, most commonly to the liver, brain, bones, and  adrenal glands (small hormone-producing glands located on top of each kidney). After diagnosis, most people with small cell lung cancer survive for about 1 year; less than seven percent survive 5 years.</p><p>Non-small cell lung cancer is divided into three main subtypes: adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Adenocarcinoma arises from the cells that line the small air sacs (alveoli) located throughout the lungs. Squamous cell carcinoma arises from squamous cells that line the passages leading from the windpipe (trachea) to the lungs (bronchi). Large cell carcinoma arises from epithelial cells that line the lungs. Large cell carcinoma encompasses non-small cell lung cancers that do not appear to be adenocarcinomas or squamous cell carcinomas. The 5-year survival rate for people with non-small cell lung cancer is usually between 11 and 17 percent; it can be lower or higher depending on the subtype and stage of the cancer.</p>",
                        "ghr_link": "https://ghr.nlm.nih.gov/condition/lung-cancer"
                    },
                    {
                        "name": "Melanoma",
                        "html_text": "<p>Melanoma is a type of skin cancer that begins in pigment-producing cells called melanocytes. This cancer typically occurs in areas that are only occasionally sun-exposed; tumors are most commonly found on the back in men and on the legs in women. Melanoma usually occurs on the skin (cutaneous melanoma), but in about 5 percent of cases it develops in melanocytes in other tissues, including the eyes (uveal melanoma) or mucous membranes that line the body's cavities, such as the moist lining of the mouth (mucosal melanoma). Melanoma can develop at any age, but it most frequently occurs in people in their fifties to seventies and is becoming more common in teenagers and young adults.</p><p>Melanoma may develop from an existing mole or other normal skin growth that becomes cancerous (malignant); however, many melanomas are new growths. Melanomas often have ragged edges and an irregular shape. They can range from a few millimeters to several centimeters across. They can also be a variety of colors: brown, black, red, pink, blue, or white.</p><p>Most melanomas affect only the outermost layer of skin (the epidermis). If a melanoma becomes thicker and involves multiple layers of skin, it can spread to other parts of the body (metastasize).</p><p>A large number of moles or other pigmented skin growths on the body, generally more than 25, is associated with an increased risk of developing melanoma. Melanoma is also a common feature of genetic syndromes affecting the skin such as xeroderma pigmentosum. Additionally, individuals who have previously had melanoma are nearly nine times more likely than the general population to develop melanoma again. It is estimated that about 90 percent of individuals with melanoma survive at least 5 years after being diagnosed.</p>",
                        "ghr_link": "https://ghr.nlm.nih.gov/condition/melanoma"
                    },
                    {
                        "name": "Ovarian Cancer",
                        "html_text": "<p>Ovarian cancer is a disease that affects women. In this form of cancer, certain cells in the ovary become abnormal and multiply uncontrollably to form a tumor. The ovaries are the female reproductive organs in which egg cells are produced. In about 90 percent of cases, ovarian cancer occurs after age 40, and most cases occur after age 60.</p><p>The most common form of ovarian cancer begins in epithelial cells, which are the cells that line the surfaces and cavities of the body. These cancers can arise in the epithelial cells on the surface of the ovary. However, researchers suggest that many or even most ovarian cancers begin in epithelial cells on the fringes (fimbriae) at the end of one of the fallopian tubes, and the cancerous cells migrate to the ovary.</p><p>Cancer can also begin in epithelial cells that form the lining of the abdomen (the peritoneum). This form of cancer, called primary peritoneal cancer, resembles epithelial ovarian cancer in its origin, symptoms, progression, and treatment. Primary peritoneal cancer often spreads to the ovaries. It can also occur even if the ovaries have been removed. Because cancers that begin in the ovaries, fallopian tubes, and peritoneum are so similar and spread easily from one of these structures to the others, they are often difficult to distinguish. These cancers are so closely related that they are generally considered collectively by experts.</p><p>In about 10 percent of cases, ovarian cancer develops not in epithelial cells but in germ cells, which are precursors to egg cells, or in hormone-producing ovarian cells called granulosa cells.</p><p>In its early stages, ovarian cancer usually does not cause noticeable symptoms. As the cancer progresses, signs and symptoms can include pain or a feeling of heaviness in the pelvis or lower abdomen, bloating, feeling full quickly when eating, back pain, vaginal bleeding between menstrual periods or after menopause, or changes in urinary or bowel habits. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a woman has ovarian cancer.</p><p>In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If ovarian cancer spreads, cancerous tumors most often appear in the abdominal cavity or on the surfaces of nearby organs such as the bladder or colon. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.</p><p>Some ovarian cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary ovarian cancers tend to develop earlier in life than non-inherited (sporadic) cases.</p><p>Because it is often diagnosed at a late stage, ovarian cancer can be difficult to treat; it leads to the deaths of about 14,000 women annually in the United States, more than any other gynecological cancer. However, when it is diagnosed and treated early, the 5-year survival rate is high.</p>",
                        "ghr_link": "https://ghr.nlm.nih.gov/condition/ovarian-cancer"
                    },
                    {
                        "name": "Wilms Tumor",
                        "html_text": "<p>Wilms tumor is a form of kidney cancer that primarily develops in children. Nearly all cases of Wilms tumor are diagnosed before the age of 10, with two-thirds being found before age 5.</p><p>Wilms tumor is often first noticed because of abdominal swelling or a mass in the kidney that can be felt upon physical examination. Some affected children have abdominal pain, fever, a low number of red blood cells (anemia), blood in the urine (hematuria), or high blood pressure (hypertension). Additional signs of Wilms tumor can include loss of appetite, weight loss, nausea, vomiting, and tiredness (lethargy).</p><p>Wilms tumor can develop in one or both kidneys. About 5 to 10 percent of affected individuals develop multiple tumors in one or both kidneys. Wilms tumor may spread from the kidneys to other parts of the body (metastasize). In rare cases, Wilms tumor does not involve the kidneys and occurs instead in the genital tract, bladder, abdomen, chest, or lower back. It is unclear how Wilms tumor develops in these tissues.</p><p>With proper treatment, children with Wilms tumor have a 90 percent survival rate. However, the risk that the cancer will come back (recur) is between 15 and 50 percent, depending on traits of the original tumor. Tumors usually recur in the first 2 years following treatment and develop in the kidneys or other tissues, such as the lungs. Individuals who have had Wilms tumor may experience related health problems or late effects of their treatment in adulthood, such as decreased kidney function, heart disease, and development of additional cancers.</p>",
                        "ghr_link": "https://ghr.nlm.nih.gov/condition/wilms-tumor"
                    }
                ]
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    "genomics_england_panelapp": {
        "version": "may_2019",
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                            "name": "Rare Disease 100K"
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                    27881370,
                    28297620
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            },
            {
                "genecolorreview": "Green",
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                "genelistname": "Familial_rhabdomyosarcoma.PanelApp.20190506",
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                            "name": "Familial rhabdomyosarcoma or sarcoma"
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                            "id": 18446744073709551615,
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                            "description": "Rare Disease 100K",
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                "pub_med_references": null
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                "genelistname": "Familial_breast_cancer.PanelApp.20190506",
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                    ],
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                    "Osteosarcoma, 259500",
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                    "Nasopharyngeal carcinoma, 607107",
                    "Pancreatic cancer, 260350",
                    "Adrenal cortical carcinoma, 202300",
                    "Breast cancer, 114480",
                    "{Basal cell carcinoma 7}, 614740",
                    "{Glioma susceptibility 1}, 137800",
                    "High Risk Breast Cancer",
                    "Breast and Ovarian Cancer"
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            {
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                "modeofinheritance": "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
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                            "id": 18446744073709551615,
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            "name": "ENST00000604348.1",
            "strand": "-",
            "gene_symbol": null,
            "chromo": "chr17",
            "position": 7578480,
            "length": 12326,
            "mrna_length": 568,
            "coding_length": 429,
            "canonical": null,
            "cytoband": "17p13.1",
            "ensembl_support_level": "4"
        },
        {
            "name": "ENST00000503591.1",
            "strand": "-",
            "gene_symbol": null,
            "chromo": "chr17",
            "position": 7578547,
            "length": 12199,
            "mrna_length": 565,
            "coding_length": 381,
            "canonical": null,
            "cytoband": "17p13.1",
            "ensembl_support_level": "5"
        }
    ],
    "weill_cornell_medicine_pmkb": {
        "version": "dec_2018",
        "items": [
            {
                "tier": 1,
                "definition": [
                    "TP53 copy number loss"
                ],
                "interpretations": "TP53 is a well known tumor suppressor gene that is mutated in wide variety of cancers. Loss of function mutations (missense, nonsense and frameshift mutations) of TP53 have been described in 10-20% of CLL cases and TP53 gene defects tend to be enriched among cases with unmutated IGH variable regions; in some series, TP53 mutations have been reported in approximately 15%-18% of IGHV unmutated CLL cases . TP53 mutations appears to be less common in other types of CLL (eg, less than 5% of IGHV3-21-expressing CLL carried a TP53 defect according to one study). Mutations of TP53 in CLL have been found together with del17p and mutations in other genes such as NOTCH1 and SF3B1.  Mutations and deletions of TP53 appear to represent  adverse prognostic markers in chronic lymphocytic leukemia.    ",
                "tissues": [
                    "Blood",
                    "Bone Marrow",
                    "Lymph Node"
                ],
                "tumour_types": [
                    "Acute Myeloid Leukemia",
                    "Atypical Chronic Myeloid Leukemia",
                    "B Lymphoblastic Leukemia/Lymphoma",
                    "Chronic Myeloid Leukemia",
                    "Chronic Myelomonocytic Leukemia",
                    "Chronic Neutrophilic Leukemia",
                    "Essential Thrombocythemia",
                    "Histiocytic and Dendritic Cell Neoplasms",
                    "Langerhans Cell Histiocytosis",
                    "Mast Cell Neoplasm",
                    "MDS with Ring Sideroblasts",
                    "Myelodysplastic Syndrome",
                    "Myeloproliferative Neoplasm",
                    "Polycythemia Vera",
                    "Primary Myelofibrosis",
                    "T Lymphoblastic Leukemia/Lymphoma",
                    "Leukocytosis",
                    "Thrombocytosis",
                    "Monocytosis",
                    "Cytopenia",
                    "Other Acute Leukemia",
                    "Acute Leukemia of Unspecified Cell Type",
                    "Anemia",
                    "Unspecified",
                    "Leukopenia",
                    "Thrombocytopenia",
                    "Eosinophilia",
                    "Myelodysplastic/Myeloproliferative Neoplasm",
                    "Myeloid Neoplasm",
                    "Polycythemia"
                ],
                "disease_or_trait": null,
                "pub_med_references": [
                    23297687,
                    23334668,
                    23403321,
                    24487413,
                    24619868,
                    24652989,
                    24725250,
                    24943832
                ],
                "variants": [
                    {
                        "type": "copy number loss",
                        "gene_id": 33956,
                        "definition": "TP53 copy number loss"
                    }
                ]
            },
            {
                "tier": 1,
                "definition": [
                    "TP53 copy number loss"
                ],
                "interpretations": "TP53 is a well known tumor suppressor gene that is mutated in wide variety of cancers.  In terms of myeloid disorders, missense, nonsense, and frameshift mutations of TP53 tend to occur in the DNA binding domain and have been reported in approximately 4% of cases of AML where they tend to be associated with a poorer prognosis and an adverse cytogenetic risk profile. TP53 mutations also occur in approximately 10% of patients with myelodysplastic syndrome (MDS) and are often associated with poorer prognosis, adverse cytogenetic profile and deletion of 5q either in isolation or as part of a complex karyotype. ",
                "tissues": [
                    "Blood",
                    "Bone Marrow"
                ],
                "tumour_types": [
                    "Acute Myeloid Leukemia",
                    "Myelodysplastic Syndrome"
                ],
                "disease_or_trait": null,
                "pub_med_references": [
                    23297687,
                    23334668,
                    23403321,
                    24487413,
                    24619868,
                    24652989,
                    24725250,
                    24943832
                ],
                "variants": [
                    {
                        "type": "copy number loss",
                        "gene_id": 33956,
                        "definition": "TP53 copy number loss"
                    }
                ]
            },
            {
                "tier": 1,
                "definition": [
                    "TP53 copy number loss"
                ],
                "interpretations": " TP53 is a well known tumor suppressor gene that is mutated in wide variety of cancers.  Among cases of acute lymphoblastic leukemia, overall TP53 mutations are reported to occur in less than 10% of cases.  However, TP53 mutations have a very high prevalence (approximately 90%) among cases of ALL with low hypodiploid karyotype and in this setting are often associated with monosomy 17 and may be associated with germline TP53 mutations in a significant proportion of such cases in children. ",
                "tissues": [
                    "Blood",
                    "Bone Marrow"
                ],
                "tumour_types": [
                    "B Lymphoblastic Leukemia/Lymphoma"
                ],
                "disease_or_trait": null,
                "pub_med_references": [
                    23297687,
                    23334668,
                    23403321,
                    24487413,
                    24619868
                ],
                "variants": [
                    {
                        "type": "copy number loss",
                        "gene_id": 33956,
                        "definition": "TP53 copy number loss"
                    }
                ]
            },
            {
                "tier": 1,
                "definition": [
                    "TP53 any mutation"
                ],
                "interpretations": "TP53 encodes p53, a tumor suppressor protein that consists of transactivation domain, proline-rich domain, DNA-binding domain, oligomerization domain, and regulatory domain. p53 responds to diverse cellular stresses to maintain genomic stability and to induce cell cycle arrest, apoptosis, DNA repair and metabolic changes. TP53 mutations represent an important mechanism of resistance to DNA-damaging chemotherapeutic agents.  Somatic TP53 mutations are found in a variety of cancers with various frequencies depending on cancer type; overall, TP53 is mutated in over one-half of human cancers. Missense mutations were the most frequent (~70-80%), followed by frameshift and nonsense mutations.  Most TP53 mutations are clustered in the DNA-binding domain encompassing exons 5 and 8. These mutations either directly disrupt the DNA-binding domain of TP53 or cause conformational changes of the TP53 protein, thus leading to severely impaired TP53 function. Overall in myeloid malignancies, TP53 mutations are found in 5% to 15% of de novo MDS and AML but 20% of myelodysplastic syndrome with isolated del(5q) and ~50% of MDS/AML with complex karyotype. TP53 mutations are also more frequent in therapy-associated myeloid neoplasm (21-38%) compared to de novo MDS and AML.   TP53 mutations are also found in 8% of blastic plasmacytoid dendritic cell neoplasm, and less than 5% in myeloproliferative neoplasms (ET, PV and PMF) and chronic myelomonocytic leukemia. TP53 mutations are independently associated with a poor prognosis in myelodysplastic syndrome (NCCN Guidelines for Myelodysplastic Syndromes) and is a poor risk factor in AML (NCCN Guildelines for AML). TP53 mutations are also associated with resistance to lenalidomide or relapse during lenalidomide treatment.   TP53 mutations are independently associated with unfavorable outcomes and shorter survival after hematopoietic stem cell transplantation in patients with myelodysplastic syndrome and myelodysplastic syndrome/acute myeloid leukemia, but an increased response to decitabine in patients with myelodysplastic syndrome or acute myeloid leukemia.\n\n",
                "tissues": [
                    "Blood",
                    "Bone Marrow"
                ],
                "tumour_types": [
                    "Acute Myeloid Leukemia",
                    "Atypical Chronic Myeloid Leukemia",
                    "B Lymphoblastic Leukemia/Lymphoma",
                    "Chronic Myeloid Leukemia",
                    "Chronic Myelomonocytic Leukemia",
                    "Chronic Neutrophilic Leukemia",
                    "Essential Thrombocythemia",
                    "Histiocytic and Dendritic Cell Neoplasms",
                    "Langerhans Cell Histiocytosis",
                    "Mast Cell Neoplasm",
                    "MDS with Ring Sideroblasts",
                    "Myelodysplastic Syndrome",
                    "Myeloproliferative Neoplasm",
                    "Polycythemia Vera",
                    "Primary Myelofibrosis",
                    "T Lymphoblastic Leukemia/Lymphoma",
                    "Leukocytosis",
                    "Thrombocytosis",
                    "Monocytosis",
                    "Cytopenia",
                    "Other Acute Leukemia",
                    "Acute Leukemia of Unspecified Cell Type",
                    "Anemia",
                    "Unspecified",
                    "Leukopenia",
                    "Thrombocytopenia",
                    "Eosinophilia",
                    "Myelodysplastic/Myeloproliferative Neoplasm",
                    "Myeloid Neoplasm",
                    "Polycythemia"
                ],
                "disease_or_trait": null,
                "pub_med_references": [
                    18596741,
                    21519010,
                    21714678,
                    22052707,
                    23690417,
                    24072100,
                    25952993,
                    26618142,
                    27288520,
                    27463065,
                    27601546,
                    27959731,
                    27967292,
                    29296692
                ],
                "variants": [
                    {
                        "type": "any mutation",
                        "gene_id": 33956,
                        "definition": "TP53 any mutation"
                    }
                ]
            },
            {
                "tier": 2,
                "definition": [
                    "TP53 any mutation"
                ],
                "interpretations": "Somatic mutations in TP53 are frequent in human cancer.  Germline TP53 mutations cause of Li-Fraumeni syndrome, which is associated with a range of early-onset cancers. The types and positions of TP53 mutations are diverse.  TP53 mutations may be potential prognostic and predictive markers in some tumor types, as well as targets for pharmacological intervention in some clinical settings. The IARC TP53 Database (http://www-p53.iarc.fr/) is a useful resource which catalogues TP53 mutations found in cancer.",
                "tissues": [
                    "Skin"
                ],
                "tumour_types": [
                    "Melanoma"
                ],
                "disease_or_trait": null,
                "pub_med_references": [
                    20182602
                ],
                "variants": [
                    {
                        "type": "any mutation",
                        "gene_id": 33956,
                        "definition": "TP53 any mutation"
                    }
                ]
            },
            {
                "tier": 2,
                "definition": [
                    "TP53 any mutation"
                ],
                "interpretations": "Somatic mutations in TP53 are frequent in human cancer.  Germline TP53 mutations cause of Li-Fraumeni syndrome, which is associated with a range of early-onset cancers. The types and positions of TP53 mutations are diverse.  TP53 mutations may be potential prognostic and predictive markers in some tumor types, as well as targets for pharmacological intervention in some clinical settings. The IARC TP53 Database (http://www-p53.iarc.fr/) is a useful resource which catalogues TP53 mutations found in cancer.",
                "tissues": [
                    "Appendix",
                    "Colon",
                    "Rectum"
                ],
                "tumour_types": [
                    "Adenocarcinoma"
                ],
                "disease_or_trait": null,
                "pub_med_references": [
                    20182602
                ],
                "variants": [
                    {
                        "type": "any mutation",
                        "gene_id": 33956,
                        "definition": "TP53 any mutation"
                    }
                ]
            },
            {
                "tier": 2,
                "definition": [
                    "TP53 any mutation"
                ],
                "interpretations": "Somatic mutations in TP53 are frequent in human cancer.  Germline TP53 mutations cause of Li-Fraumeni syndrome, which is associated with a range of early-onset cancers. The types and positions of TP53 mutations are diverse.  TP53 mutations may be potential prognostic and predictive markers in some tumor types, as well as targets for pharmacological intervention in some clinical settings. The IARC TP53 Database (http://www-p53.iarc.fr/) is a useful resource which catalogues TP53 mutations found in cancer.",
                "tissues": [
                    "Brain"
                ],
                "tumour_types": [
                    "Glioblastoma"
                ],
                "disease_or_trait": null,
                "pub_med_references": [
                    20182602
                ],
                "variants": [
                    {
                        "type": "any mutation",
                        "gene_id": 33956,
                        "definition": "TP53 any mutation"
                    }
                ]
            },
            {
                "tier": 2,
                "definition": [
                    "TP53 copy number loss",
                    "TP53 any deletion"
                ],
                "interpretations": "P53 activates the transcription of genes involved in cell cycle arrest, DNA repair, and apoptosis. Deletion and point mutation at the TP53 locus occur in 25%-40% and 5%-40% of prostate cancer, respectively. Although the frequency of p53 mutations seems to be lower in prostate cancer than in other cancers, these alterations are not exclusively late events, as they have been shown in 25% to 30% of clinically localized prostate cancer. Several studies indicate that p53 overexpression may be associated with poor prognosis, especially when present in combination with Bcl2. Interestingly, SPOP mutations are also mutually exclusive with deletions and mutations in the TP53 tumor suppressor.\n",
                "tissues": [
                    "Prostate"
                ],
                "tumour_types": [
                    "Adenocarcinoma"
                ],
                "disease_or_trait": null,
                "pub_med_references": [
                    23759327,
                    26695660
                ],
                "variants": [
                    {
                        "type": "copy number loss",
                        "gene_id": 33956,
                        "definition": "TP53 copy number loss"
                    },
                    {
                        "type": "any mutation",
                        "gene_id": 33956,
                        "coding_impact": "deletion",
                        "definition": "TP53 any deletion"
                    }
                ]
            },
            {
                "tier": 2,
                "definition": [
                    "TP53 any mutation"
                ],
                "interpretations": "Somatic mutations in TP53 are frequent in human cancer.  Germline TP53 mutations cause of Li-Fraumeni syndrome, which is associated with a range of early-onset cancers. The types and positions of TP53 mutations are diverse.  TP53 mutations may be potential prognostic and predictive markers in some tumor types, as well as targets for pharmacological intervention in some clinical settings. The IARC TP53 Database (http://www-p53.iarc.fr/) is a useful resource which catalogues TP53 mutations found in cancer.",
                "tissues": [
                    "Skin"
                ],
                "tumour_types": [
                    "Langerhans Cell Histiocytosis"
                ],
                "disease_or_trait": null,
                "pub_med_references": [
                    20182602
                ],
                "variants": [
                    {
                        "type": "any mutation",
                        "gene_id": 33956,
                        "definition": "TP53 any mutation"
                    }
                ]
            },
            {
                "tier": 2,
                "definition": [
                    "TP53 any mutation"
                ],
                "interpretations": "Somatic mutations in TP53 are frequent in human cancer. Germline TP53 mutations cause of Li-Fraumeni syndrome, which is associated with a range of early-onset cancers. The types and positions of TP53 mutations are diverse. TP53 mutations may be potential prognostic and predictive markers in some tumor types, as well as targets for pharmacological intervention in some clinical settings. The IARC TP53 Database (http://www-p53.iarc.fr/) is a useful resource which catalogues TP53 mutations found in cancer.",
                "tissues": [
                    "Adrenal Gland",
                    "Anus",
                    "Ampulla (Pancreaticobiliary Duct)",
                    "Appendix",
                    "Bladder",
                    "Blood",
                    "Bone",
                    "Bone Marrow",
                    "Brain",
                    "Breast",
                    "Spinal Cord",
                    "Cervix",
                    "Chest Wall",
                    "Colon",
                    "Endometrium",
                    "Esophagus",
                    "Eye",
                    "Fallopian Tube",
                    "Fibroadipose Tissue",
                    "Gall Bladder",
                    "Kidney",
                    "Larynx",
                    "Liver",
                    "Lung",
                    "Lymph Node",
                    "Nasal Cavity",
                    "Oral Cavity",
                    "Ovary",
                    "Pancreas",
                    "Parathyroid",
                    "Penis",
                    "Peripheral Nervous System",
                    "Peritoneum",
                    "Pharynx",
                    "Pituitary",
                    "Placenta",
                    "Pleura",
                    "Prostate",
                    "Retroperitoneum",
                    "Salivary Gland",
                    "Seminal Vesicle",
                    "Skeletal Muscle",
                    "Skin",
                    "Small Intestine",
                    "Soft Tissue",
                    "Spleen",
                    "Stomach",
                    "Testis",
                    "Thymus",
                    "Thyroid",
                    "Tonsil",
                    "Ureter",
                    "Uterus",
                    "Vagina",
                    "Rectum",
                    "Cartilage",
                    "Blood Vessel",
                    "Buccal Swab",
                    "Heart",
                    "Trachea",
                    "Salivary Duct",
                    "Spermatic Cord",
                    "Vulva",
                    "Infratentorial",
                    "Supratentorial",
                    "Gastroesophageal Junction",
                    "Sellar",
                    "Suprasellar"
                ],
                "tumour_types": [
                    "Acinar Cell Carcinoma",
                    "Acinic Cell Carcinoma",
                    "Adenocarcinoma",
                    "Adenoid Cystic Carcinoma",
                    "Adenosarcoma",
                    "Ameloblastic Tumor",
                    "Anaplastic Large Cell Lymphoma",
                    "Angioimmunoblastic T-Cell Lymphoma",
                    "Angiomatoid Fibrous Histiocytoma",
                    "Angiomatosis",
                    "Angiomyolipoma",
                    "Angiosarcoma",
                    "Astrocytoma",
                    "Anaplastic",
                    "Basal Cell Carcinoma",
                    "Burkitt Lymphoma",
                    "Carcinoid Tumor",
                    "Carcinoma",
                    "Carcinosarcoma",
                    "Cholangiocarcinoma",
                    "Chondrosarcoma",
                    "Chordoma",
                    "Choriocarcinoma",
                    "Chromophobe Renal Cell Carcinoma",
                    "Chronic Lymphocytic Leukemia",
                    "Classical Hodgkin Lymphoma",
                    "Clear Cell Carcinoma",
                    "Clear Cell Renal Cell Carcinoma",
                    "Craniopharyngioma",
                    "Dermatofibrosarcoma",
                    "Desmoplastic Small Round Cell Tumor",
                    "Diffuse Large B Cell Lymphoma",
                    "Ductal Carcinoma",
                    "Ependymoma",
                    "Ewing Sarcoma",
                    "Fibromatosis",
                    "Follicular Carcinoma",
                    "Follicular Lymphoma",
                    "Gastrointestinal Stromal Tumor",
                    "Germ Cell Tumor",
                    "Giant Cell Tumor",
                    "Glioblastoma",
                    "Glomus Tumor",
                    "Granular Cell Tumor",
                    "Hairy Cell Leukemia",
                    "Hemangioendothelioma",
                    "Hepatocellular Carcinoma",
                    "Invasive Ductal Carcinoma",
                    "Kaposi Sarcoma",
                    "Leiomyoma",
                    "Leiomyosarcoma",
                    "Lipoma",
                    "Liposarcoma",
                    "Lobular Carcinoma",
                    "Lymphoplasmacytic Lymphoma",
                    "Malignant Mullerian Mixed Tumor",
                    "Mantle Cell Lymphoma",
                    "Marginal Zone B Cell Lymphoma",
                    "Medullary Carcinoma",
                    "Medulloblastoma",
                    "Melanoma",
                    "Meningioma",
                    "Merkel Cell Carcinoma",
                    "Mesothelioma",
                    "Mucinous Tumors of Appendix",
                    "Mucinous Tumors of Ovary",
                    "Mucoepidermoid Carcinoma",
                    "Myxofibrosarcoma",
                    "Nasopharyngeal Carcinoma",
                    "Neuroblastoma",
                    "Neuroendocrine Carcinoma",
                    "Neuroendocrine Neoplasm",
                    "NK Cell Lymphoproliferative Disorder",
                    "NLPHL",
                    "Non-Small Cell Lung Carcinoma",
                    "Oligodendroglioma",
                    "Osteosarcoma",
                    "Papillary Carcinoma",
                    "Papillary Renal Cell Carcinoma",
                    "Peripheral T Cell Lymphoma",
                    "Pheochromocytoma",
                    "Plasma Cell Disorder",
                    "Post-Transplant Lymphoproliferative Disorder",
                    "Primitive Neuroectodermal Tumor",
                    "Renal Cell Carcinoma",
                    "Reninoma",
                    "Retinoblastoma",
                    "Rhabdomyosarcoma",
                    "Sarcoma",
                    "Schwannoma",
                    "Serous Carcinoma",
                    "Sex Cord Stromal Tumor",
                    "Small Cell Carcinoma",
                    "Solid Pseudopapillary Tumor of Pancreas",
                    "Spindle Cell Neoplasm",
                    "Squamous Cell Carcinoma",
                    "T Cell Lymphoproliferative Disorder",
                    "T-Cell LGL Leukemia",
                    "Thymic Carcinoma",
                    "Thymoma",
                    "Urothelial Carcinoma",
                    "Tumors of Peripheral Nerves",
                    "Wilms Tumor",
                    "Pilocytic",
                    "Ganglioglioma",
                    "Neuroepithelial Neoplasm",
                    "NOS",
                    "Pleomorphic Carcinoma",
                    "Solitary Fibrous Tumor",
                    "Neuroepithelial neoplasm",
                    "high grade",
                    "Diffusely Infiltrating",
                    "Diffuse Midline Glioma",
                    "Infiltrating Glioma",
                    "Intraductal Papillary Mucinous Neoplasm (IPMN)",
                    "Lymphadenopathy",
                    "Lymphocytosis",
                    "Symptomatic",
                    "Monoclonal Gammopathy",
                    "Mucinous or Serous Cystic Neoplasms of Pancreas",
                    "Mycosis Fungoides",
                    "Unspecified Site",
                    "Pleomorphic Xanthoastrocytoma",
                    "Rash and Other Nonspecific Skin Eruption"
                ],
                "disease_or_trait": null,
                "pub_med_references": [
                    20182602
                ],
                "variants": [
                    {
                        "type": "any mutation",
                        "gene_id": 33956,
                        "definition": "TP53 any mutation"
                    }
                ]
            }
        ]
    },
    "unil_domino": {
        "version": "version_1",
        "lda_score": 2.7493300000000005,
        "numberdonor_numbersynonymous": 0.0,
        "phylop_at_5_prime_utr": 0.5294619999999999,
        "probability_of_ad": 0.999028,
        "string_combined_score": 8,
        "string_experimental_score": 3,
        "string_text_mining_score": 3,
        "mrna_half_life": 0
    }
}