Cancer
Neoplasm of Uncertain Histogenesis
CI-CAN-00000034Explore in graph →
Non-malignant20,291 active trials259 approved drugs3,814 evidence items
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Cancer
CI-CAN-00000034Explore in graph →
Variants & evidence
7,620 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| TP53 ALTERATION2 | ||||||||
| (prognostic) | Rhabdomyosarcoma | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID9594This study evaluated 641 cases of rhabdomyosarcoma (RMS) that were enrolled in the Children’s Oncology Group (COG) trials from 1998 to 2017 and the UK malignant mesenchymal tumor and RMS2005 trails fr… (full text at CIViC) PMID 34166060 · Shern et al., 2021 · Open in CIViC | civic |
| Carboplatin + CisplatinSubstitutes | Malignant Ovarian Neoplasm | Predictive | B | Supports Resistance | 4 | accepted | EID2771In a group of patients with invasive ovarian carcinoma who had undergone surgery, a subset of 74 patients treated with platinum based chemotherapy were assessed for p53 alteration (p53 mutation or p5… (full text at CIViC) PMID 11595686 · Reles et al., 2001 · Open in CIViC | civic |
| TP53BP1 D353E1 | ||||||||
| (predisposing) | Malignant Lung Neoplasm | Predisposing | E | N/A N/A | 2 | submitted | EID8046UK Caucasians were enrolled in a large-scale GWAS study looking for loci associated with lung cancer susceptibility (1529 cases and 2707 controls). Of 64 nonsynonymous, single nucleotide polymorphisms… (full text at CIViC) PMID 16741161 · Rudd et al., 2006 · Open in CIViC | civic |
| TP53 C135F1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | submitted | EID10076A subset of 58 cancer cell lines with unaltered TP53 are sensitive to MDM2 inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 inhibitor.… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| TP53 C135fs1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | submitted | EID10073Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| TP53 C238Y1 | ||||||||
| (prognostic) | Malignant Breast Neoplasm | Prognostic | E | Supports Poor Outcome | 3 | accepted | EID7173Cys-238 was directly bound to zinc molecule. Patients with missense mutations affecting amino acids directly involved in DNA or zinc binding displayed a very aggressive clinical phenotype. When patien… (full text at CIViC) PMID 11051239 · Alsner et al., 2000 · Open in CIViC | civic |
| TP53 CONSERVED DOMAIN MUT1 | ||||||||
| (prognostic) | Malignant Ovarian Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID2993Patients 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 u… (full text at CIViC) PMID 11595686 · Reles et al., 2001 · Open in CIViC | civic |
| TP53 D281G1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID7122Human mutant D281G p53 was stably transfected into the murine fibroblast (10)3 and human osteosarcoma SAOS-2 cell lines, which lack endogenous p53 expression, resulting in viable cells. In contrast, p… (full text at CIViC) PMID 8099841 · Dittmer et al., 1993 · Open in CIViC | civic |
| TP53 Deleterious Mutation7 | ||||||||
| (prognostic) | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Does Not Support Poor Outcome | 4 | accepted | EID1147Pooled 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; HR… (full text at CIViC) PMID 26899019 · Ma et al., 2016 · Open in CIViC | civic |
| 〃 | Head and Neck Squamous Cell Carcinoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID517In 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 witho… (full text at CIViC) PMID 22090360 · Skinner et al., 2012 · Open in CIViC | civic |
| Adjuvant Chemotherapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | |||||||
| TP53 DNA Binding Domain Mutation2 | ||||||||
| (prognostic) | Oral Cavity Squamous Cell CarcinomaALIAS | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID641Oral 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 mutati… (full text at CIViC) PMID 12509970 · Yamazaki et al., 2003 · Open in CIViC | civic |
| Tamoxifen | Malignant Breast Neoplasm | Predictive | B | Supports Resistance | 3 | accepted | EID2783In 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 … (full text at CIViC) PMID 10786679 · Berns et al., 2000 · Open in CIViC | civic |
| TP53 G244R1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | submitted | EID10072Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| TP53 G245S1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID4883Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| TP53 H193R1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | submitted | EID10063Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| TP53 I251T1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | submitted | EID10075Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| TP53 K132Q1 | ||||||||
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | submitted | EID10065Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| TP53 L3 Domain Mutation2 | ||||||||
| (prognostic) | Malignant Colorectal NeoplasmCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID3041A prospective study was performed using tumor and normal tissue from 160 colorectal cancer patients undergoing resection. 68 of 160 patients showed tumor p53 mutation, and 18 of 68 cases showed mutati… (full text at CIViC) PMID 12433709 · Russo et al., 2002 · Open in CIViC | civic |
| Tamoxifen | Malignant Breast Neoplasm | Predictive | B | Supports Resistance | 3 | submitted | EID3036In a study of 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 respo… (full text at CIViC) PMID 10786679 · Berns et al., 2000 · Open in CIViC | civic |
| TP53 Loss1 | ||||||||
| Docetaxel | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID1146A 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-beari… (full text at CIViC) PMID 22425996 · Chen et al., 2012 · Open in CIViC | civic |
| TP53 M237I3 | ||||||||
| Unspecified therapy | GlioblastomaCURATED_BROADER | Predictive | C | Supports N/A | 5 | submitted | EID8064mutants in diverse tumor types activate different p53 target genes, but some may give rise to the same GoF phenotype. 12,13 For example, M237I, in glioblastoma, and R282W, in lung cancer, trigger chem… (full text at CIViC) PMID 29260852 · Silva et al., 2018 · Open in CIViC | civic |
| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 3 | accepted | EID4885Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 115 cancer cell lines with TP53 mutation and absence of WT allele are sensitive to MDM2 Inhibitor. TP… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| Temozolomide | GlioblastomaCURATED_BROADER | |||||||
| TP53 Mutation22 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | A | Supports Poor Outcome | 5 | accepted | EID1507In 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). PMID 26837699 · Nadeu et al., 2016 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID1452The 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.… (full text at CIViC) PMID 20697090 · Zenz et al., 2010 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 5 | accepted | ||
Data updated 1 hour agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Predictive |
| B |
| Does Not Support Sensitivity Response |
| 2 |
| accepted |
EID1148Pooled 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 … (full text at CIViC) PMID 26899019 · Ma et al., 2016 · Open in CIViC |
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| MDM2 Inhibitor AMGMDS3 | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID2967MDM2 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 th… (full text at CIViC) PMID 25730903 · Saiki et al., 2015 · Open in CIViC | civic |
| Pazopanib | Sarcoma | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID117019 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… (full text at CIViC) PMID 26646755 · Koehler et al., 2016 · Open in CIViC | civic |
| Rebemadlin | Malignant NeoplasmALIAS | Predictive | D | Supports Resistance | 4 | accepted | EID2968MDM2 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 … (full text at CIViC) PMID 17671205 · Efeyan et al., 2007 · Open in CIViC | civic |
| RG7112 | Leukemia | Predictive | B | Supports Resistance | 3 | accepted | EID2966Phase 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… (full text at CIViC) PMID 26459177 · Andreeff et al., 2016 · Open in CIViC | civic |
| Predictive |
| D |
| Supports Resistance |
| 3 |
| submitted |
EID7979The glioblastoma T98G cell line possesses a TP53 M237I variant. This cell line initially exhibited resistance to temozolomide treatment, but a five-fold increase in chemosensitivity (IC50 112.15 ug/ml… (full text at CIViC) PMID 24248532 · Wang et al., 2014 · Open in CIViC |
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EID1485In 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… (full text at CIViC) PMID 24943832 · Baliakas et al., 2015 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports N/A | 5 | accepted | EID2999A 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 encompa… (full text at CIViC) PMID 28453411 · Shepherd et al., 2017 · Open in CIViC | civic |
| (predisposing) | Medulloblastoma, SHH-Activated, TP53-MutantALIAS | Predisposing | B | Supports Predisposition | 5 | submitted | EID8346This international, multicenter study analyzed patients with medulloblastoma (MB) from both retrospective and prospective cohorts in order to identify consensus MB predisposition genes. A total of 102… (full text at CIViC) PMID 29753700 · Waszak et al., 2018 · Open in CIViC | civic |
| (prognostic) | Medulloblastoma, SHH-Activated | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID8347In the childhood (≥4.3 years) SHH-MB subgroup, TP53 mutations (n=13) are associated with shorter progression-free survival (PFS) compared to the no mutation group (n=35) (HR, 3.47; 95% CI, 1.29 to 9.3… (full text at CIViC) PMID 28545823 · Schwalbe et al., 2017 · Open in CIViC | civic |
| 〃 | Esophageal Squamous Cell CarcinomaALIAS | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID519In a retrospective study of patients with esophageal carcinoma, those with mutations in TP53 had worse overall survival. PMID 19941080 · Yamasaki et al., 2010 · Open in CIViC | civic |
| 〃 | B Lymphoblastic Leukemia/LymphomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID520In 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… (full text at CIViC) PMID 22699455 · Krentz et al., 2013 · Open in CIViC | civic |
| 〃 | Myelodysplastic SyndromeCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID521In patients with myelodysplastic syndrome, in a multivariate analysis those with mutations in TP53 had shorter overall survival than wild-type patients. PMID 24836762 · Bally et al., 2014 · Open in CIViC | civic |
| 〃 | Head and Neck Squamous Cell Carcinoma | Prognostic | B | Does Not Support Poor Outcome | 4 | accepted | EID523Tumors 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 … (full text at CIViC) PMID 11325447 · Alsner et al., 2001 · Open in CIViC | civic |
| 〃 | Head and Neck Squamous Cell Carcinoma | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID524Tumors 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 l… (full text at CIViC) PMID 11325447 · Alsner et al., 2001 · Open in CIViC | civic |
| 〃 | B Lymphoblastic Leukemia/LymphomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID640In 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 … (full text at CIViC) PMID 21747090 · Hof et al., 2011 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID1018In 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 … (full text at CIViC) PMID 26771088 · Middeke et al., 2016 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID1451In 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 … (full text at CIViC) PMID 18689542 · Zenz et al., 2008 · Open in CIViC | civic |
| 〃 | Myelodysplastic SyndromeCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID6943In a study of 439 patients with myelodysplastic syndrome, patients with TP53 mutations (N=33) has worse overall survival than wildtype patients (N=406) (P<0.001 univariate). This difference was also o… (full text at CIViC) PMID 21714648 · Bejar et al., 2011 · Open in CIViC | civic |
| 〃 | MedulloblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID7963This study showed that patients with TP53 mutated medulloblastoma (8/49, 16%) exhibited worse prognosis compared to those with wildtype medulloblastoma (41/49, 84%). A 5-year overall survival of 0% wa… (full text at CIViC) PMID 20142599 · Tabori et al., 2010 · Open in CIViC | civic |
| 〃 | MedulloblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID7964This study examined the prognostic implication of TP53 mutation status in different molecular subgroups of medulloblastoma. A discovery cohort of 397 patients and a validation cohort of 156 cases were… (full text at CIViC) PMID 23835706 · Zhukova et al., 2013 · Open in CIViC | civic |
| (diagnostic) | Medulloblastoma, SHH-Activated, TP53-MutantALIAS | Diagnostic | B | Supports Positive | 4 | submitted | EID8345One of the goals of this study is to understand the biology of the sonic-hedgehog subgroup of medulloblastoma (SHH-MB) across different age groups. A large cohort of patients (n=133) with SHH-MB, incl… (full text at CIViC) PMID 24651015 · Kool et al., 2014 · Open in CIViC | civic |
| (prognostic) | Malignant Breast Neoplasm | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID393In breast cancer patients harboring TP53 mutation, mutations in conserved regions such as R249 are prognostic for a worse overall survival compared to those harboring wild-type TP53. Multivariate Cox … (full text at CIViC) PMID 9569050 · Berns et al., 1998 · Open in CIViC | civic |
| 〃 | Head and Neck Squamous Cell Carcinoma | Prognostic | B | Does Not Support Poor Outcome | 3 | accepted | EID518Unlike 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 mutati… (full text at CIViC) PMID 8901856 · Koch et al., 1996 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID1450A 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 pat… (full text at CIViC) PMID 8241511 · el Rouby et al., 1993 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID1478In 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%),… (full text at CIViC) PMID 21483000 · Gonzalez et al., 2011 · Open in CIViC | civic |