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Variants & evidence
5,621 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 |
|---|---|---|---|---|---|---|---|---|
| ATM R777FS1 | ||||||||
| Doxorubicin | Chronic Lymphocytic Leukemia | Predictive | D | Supports Resistance | — | submitted | EID2842In an in vitro study using primary chronic lymphocytic leukemia (CLL) cells from patients with mutated (n=8) and wildtype (n=5) ATM, inhibition of cell growth was used as an assay to determine sensiti… (full text at CIViC) PMID 23585524 · Navrkalova et al., 2013 · Open in CIViC | civic |
| ATM T2666A1 | ||||||||
| Doxorubicin | Chronic Lymphocytic Leukemia | Predictive | D | Supports Resistance | 3 | accepted | EID2221Primary peripheral blood mononuclear cells were taken from chronic lymphocytic leukemia patients, some of whom had prior therapy. Cells were treated with doxorubicin to induce double-strand (DSB) and … (full text at CIViC) PMID 23585524 · Navrkalova et al., 2013 · Open in CIViC | civic |
| ATM Underexpression2 | ||||||||
| (prognostic) | Chronic Lymphocytic Leukemia | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID156443 B-CLL patients with LoH or reduced protein levels (<50% normal expression, radioimmunoassay, western blot) of ATM were found to have significantly shorter overall survival (35.6 vs. 97.3 months; P=… (full text at CIViC) PMID 9788599 · Starostik et al., 1998 · Open in CIViC | civic |
| Olaparib | Gastric Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID878Low ATM protein expression led to sensitivity to PARP inhibitors in TP53 -ve gastric cancer cell lines (8 lines were used for various aspects of this study). PMID 24841718 · Kubota et al., 2014 · Open in CIViC | civic |
| ATM V1268FS1 | ||||||||
| Doxorubicin | Chronic Lymphocytic Leukemia | Predictive | D | Supports Resistance | — | submitted | EID2844In an in vitro study using primary chronic lymphocytic leukemia (CLL) cells from patients with mutated (n=8) and wildtype (n=5) ATM, inhibition of cell growth was used as an assay to determine sensiti… (full text at CIViC) PMID 23585524 · Navrkalova et al., 2013 · Open in CIViC | civic |
| NRG1 Fusion1 | ||||||||
| Afatinib | Cholangiocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID5858In a single patient with presumed cholangiocarcinoma a novel ATP1B1-NRG1 gene fusion was detected. Integrative genome analysis was used to assess the potential functional significance of the gene fusi… (full text at CIViC) PMID 28950338 · Jones et al., 2017 · Open in CIViC | civic |
| NRG1 Fusion + KRAS WildtypeNRG1KRAS1 | ||||||||
| Afatinib | Pancreatic Ductal Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID7492Whole genome sequencing and transcriptomic analysis were performed on 47 advanced PDAC patients. 3/47 patients were KRAS wildtype and all three of these cases harbored a NRG1 fusion. A 59-year-old met… (full text at CIViC) PMID 31068372 · Jones et al., 2019 · Open in CIViC | civic |
| ATR Loss-of-function1 | ||||||||
| Enzalutamide + TalazoparibCombination | Castration-Resistant Prostate Carcinoma | Predictive | A | Supports Sensitivity Response | 2 | submitted | EID12217In the phase 3 TALAPRO-2 trial 805 patients with castration-resistant prostate cancer were enrolled and randomized to talazoparib or placebo plus enzalutamide treatment. Patients were tested for homol… (full text at CIViC) PMID 37285865 · Agarwal et al., 2023 · Open in CIViC | civic |
| ATRX Loss-of-function3 | ||||||||
| Adavosertib | GlioblastomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID10939ATRX deficient glioblastoma model cell lines were created using CRISPR-based gene editing to knock-out ATRX in immortalized astrocytes. ATRX knock-out cells were found to be sensitive (IC50 0.012 uM) … (full text at CIViC) PMID 34118569 · Garbarino et al., 2021 · Open in CIViC | civic |
| Olaparib + TalazoparibSubstitutes | GlioblastomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID10940ATRX deficient glioblastoma model cell lines were created using CRISPR-based gene editing to knock-out ATRX in immortalized astrocytes. ATRX knock-out cells were found to be more sensitive than wild-t… (full text at CIViC) PMID 34118569 · Garbarino et al., 2021 · Open in CIViC | civic |
| Pyridostatin | ||||||||
| ATRX Mutation2 | ||||||||
| (diagnostic) | Anaplastic AstrocytomaALIAS | Diagnostic | B | Supports Positive | 5 | submitted | EID8950293 adult cases of low grade gliomas (LGGs) underwent a variety of analyses, including but not limited to exome sequencing (289 samples), copy number profiling (285), mRNA sequencing (277) and sequenc… (full text at CIViC) PMID 26061751 · 2015, N. Engl. J. Med. · Open in CIViC | civic |
| 〃 | Anaplastic AstrocytomaALIAS | Diagnostic | B | Supports Positive | 3 | accepted | EID8868Whole exome sequencing of 4 low grade gliomas (LGGs) and targeted sequencing of 28 LGGs revealed ATRX variants are found exclusively in a subset of IDH1-mutant, 1p/19q intact LGGs. Paired blood sample… (full text at CIViC) PMID 23104868 · Kannan et al., 2012 · Open in CIViC | civic |
| ATRX Underexpression4 | ||||||||
| (prognostic) | Childhood Low Grade Glioma | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID7190Loss of ATRX was identified in 12 of 247 patients with PLGGs using immunohistochemistry. Survival analysis showed that ATRX loss was associated with adverse overall survival (p<0.0001) and progression… (full text at CIViC) PMID 29948154 · Yang et al., 2018 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Prognostic | D | Supports Poor Outcome | 4 | accepted | EID1648In a glioblastoma mouse model induced by NRAS and p53 knockdown, ATRX loss was associated with a decreased median survival (69 days vs. 84 days; P = .0032). Also, the tumors grew to a larger size at e… (full text at CIViC) PMID 26936505 · Koschmann et al., 2016 · Open in CIViC | civic |
| PCV Regimen + TemozolomideSubstitutes | Anaplastic AstrocytomaALIAS | |||||||
| ATXN1L Loss1 | ||||||||
| Dabrafenib + VemurafenibSubstitutes | Melanoma | Predictive | B | Supports Resistance | 3 | submitted | EID5124ATXN1L expression was analyzed in 30 BRAF V600-mutant untreated melanoma metastes. 21 of these patients were subsequently treated with dabrafenib or vemurafenib, and 9 of these patients were treated w… (full text at CIViC) PMID 28178529 · Wang et al., 2017 · Open in CIViC | civic |
| ATXN7 Q39P1 | ||||||||
| (oncogenic) | Thyroid Gland Carcinoma | Oncogenic | D | Supports Oncogenicity | 2 | submitted | EID9861Mutations in the polyglutamine domain of ATXN7 were identified in a forward genetic screen of HRAS G12V mutant thyroid follicular cells using a transposon-based mutagenesis system. Thyroid cancer-deri… (full text at CIViC) PMID 28584132 · Montero-Conde et al., 2017 · Open in CIViC | civic |
| AURKA Amplification1 | ||||||||
| Alisertib + CisplatinCombination | Esophageal AdenocarcinomaALIAS | Predictive | E | Supports Sensitivity Response | 3 | accepted | EID456Antitumour effect of alisertib treatment in esophageal adenocarcinomas can be intensified in combination with cisplatin. PMID 22302096 · Sehdev et al., 2012 · Open in CIViC | civic |
| AURKA EXPRESSION2 | ||||||||
| (prognostic) | Ovarian Carcinoma | Prognostic | B | Supports Better Outcome | 3 | accepted | EID416In patients with ovarian carcinomas, those with Aurora kinase A expression (as measured by immunohistochemistry) had increased progression-free and overall survival compared to those without expressio… (full text at CIViC) PMID 19157502 · Mendiola et al., 2009 · Open in CIViC | civic |
| Cisplatin + Fluorouracil + Radiation TherapyCombination | Esophageal Squamous Cell CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1653A retrospective study examining the expression of AURKA in tumor samples of 78 esophageal squamous cell carcinoma patients found that positive expression of AURKA (>10% of cells by IHC) was correlated… (full text at CIViC) PMID 25924824 · Tamotsu et al., 2015 · Open in CIViC | civic |
| AURKA Overexpression4 | ||||||||
| Alisertib + CisplatinCombination | Esophageal AdenocarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID9627The efficacy of novel AURKA inhibitor alisertib (MLN8327) was tested alone or in combination with cisplatin in three esophageal adenocarcinoma cell lines (FLO-1, OE19 and OE33) that overexpress AURKA.… (full text at CIViC) PMID 22302096 · Sehdev et al., 2012 · Open in CIViC | civic |
| Cisplatin | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID871High levels of Aurora-A expression (retrospectively assessed by IHC in 102 NSCLC patients) predicted poorer overall survival and progression free survival in a population treated with surgery and cisp… (full text at CIViC) PMID 25082261 · Xu et al., 2014 · Open in CIViC | civic |
| Paclitaxel | ||||||||
| AURKB Overexpression1 | ||||||||
| Alisertib + Barasertib + CopanlisibCombination | Head and Neck Squamous Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID10836Concurrent inhibition of both AURKB (and AURKA) and PI3K is synergistic in NOTCH1-wild type and NOTCH-1 mutant head and neck squamous cell carcinoma (HNSCC) cell lines. In NOTCH1-wt cell lines, the co… (full text at CIViC) PMID 36169922 · Shah et al., 2022 · Open in CIViC | civic |
| AXIN2 rs1433488531 | ||||||||
| (predisposing) | Chronic Lymphocytic Leukemia | Predisposing | A | Supports Protectiveness | 5 | submitted | EID12065The germline variant rs143348853 (5bp deletion), creates MEF2 transcription factor binding site, which induces activity in the locus around AXIN2 gene and associates with elevated AXIN2 expression. In… (full text at CIViC) PMID 35440565 · Llimos et al., 2022 · Open in CIViC | civic |
| AXL EXPRESSION1 | ||||||||
| (prognostic) | Esophageal Squamous Cell CarcinomaALIAS | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID1655Immunohistochemical analysis of tumors from 116 esophageal squamous cell carcinoma found that expression of AXL was associated with increased progression of the tumor (P < 0.0001), increased risk of d… (full text at CIViC) PMID 27172793 · Hsieh et al., 2016 · Open in CIViC | civic |
| B2M Loss1 | ||||||||
| Immune Checkpoint Inhibitor | Melanoma | Predictive | D | Supports Resistance | 2 | submitted | EID12152Whole exome sequencing (WES) was performed on 49 longitudinal tumour samples from 17 patients with metastatic melanoma, of whom 10 responded to ICIs/CPB, where 5 had durable responses, while 5 eventua… (full text at CIViC) PMID 29070816 · Sade-Feldman et al., 2017 · Open in CIViC | civic |
| B2M Mutation2 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11930This study used a combination of RNA-seq, whole genome and targeted sequencing to identify recurrently mutated genes in follicular and diffuse large B-cell lymphoma. They reported 30 genes that had si… (full text at CIViC) PMID 21796119 · Morin et al., 2011 · Open in CIViC | civic |
| 〃 | Mantle Cell Lymphoma | Oncogenic | E | Supports Oncogenicity | 3 | submitted | EID11891Through a meta-analysis of exome and whole genome sequencing data, this study identified 18 genes that were significantly enriched for mutations in MCL. PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC | civic |
| B2M S14FS1 | ||||||||
| Pembrolizumab | Cutaneous MelanomaALIAS | Predictive | C | Supports Resistance | 3 | accepted | EID1569Paired tumor samples were analyzed from four patients with metastatic melanoma and initial response with a subsequent relapse under pembrolizumab (PD-1 checkpoint inhibitor) therapy. Baseline biopsies… (full text at CIViC) PMID 27433843 · Zaretsky et al., 2016 · Open in CIViC | civic |
| B4GALT1 Overexpression1 | ||||||||
| (prognostic) | Renal Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID1278438 patients with non-metastatic clear-cell renal carcinoma were were retrospectively analysed for B4GALT1 expression via IHC. High B4GALT1 expression was associated with poor overall survival (P<0.00… (full text at CIViC) PMID 27092876 · Xie et al., 2016 · Open in CIViC | civic |
| FGFR1 Fusion1 | ||||||||
| Fexagratinib | Carcinoma | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID9243Phase II study (NCT02465060) from NCI-MATCH Trial (EAY131) Subprotocol W addressed the use of AZD4547 (an FGFR 1-3 inhibitor) in 48 tumor patients carrying FGFR 1-3 variants. Partial responses were ob… (full text at CIViC) PMID 32463741 · Chae et al., 2020 · Open in CIViC | civic |
| BAP1 ALTERNATIVE TRANSCRIPT (ATI)1 | ||||||||
| Apitolisib + OlaparibCombination | Malignant Mesothelioma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID5929A novel alternative splice isoform of BAP1 (BAP1Δ) that misses part of the catalytic domain showed reduced deubiquitinating activity compared with full-length BAP1. 4 MPM cell lines expressing more th… (full text at CIViC) PMID 28389374 · Parrotta et al., 2017 · Open in CIViC | civic |
| BAP1 c.122+1G>T1 | ||||||||
| (predisposing) | Meningioma | Predisposing | C | Supports Predisposition | 2 | submitted | EID13245Jadun et al. reported an adolescent girl with a skull-base meningothelial meningioma, WHO grade 1. Initial germline testing of NF2, LZTR1, and SMARCB1 was negative. Subsequent paired tumor-normal geno… (full text at CIViC) PMID 41442315 · Jadun et al., 2026 · Open in CIViC | civic |
| BAP1 EXPRESSION1 | ||||||||
| (prognostic) | Uveal Melanoma | Prognostic | B | Supports Better Outcome | 3 | accepted | EID458In patients with uveal melanoma, those with BAP1 expression (determined by immunohistochemical staining) had better survival. PMID 25147369 · van Essen et al., 2014 · Open in CIViC | civic |
| BAP1 Loss3 | ||||||||
| EPZ011989 | Pleural Malignant MesotheliomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID8329The in vivo experiment demonstrated that Bap1 loss results in increased trimethylated histone H3 lysine 27 (H3K27me3), elevated Ezh2 expression, and enhanced repression of Polycomb Repressive Complex … (full text at CIViC) PMID 26437366 · LaFave et al., 2015 · Open in CIViC | civic |
| Mocetinostat + VorinostatSubstitutes | Malignant Mesothelioma | Predictive | E | Supports Sensitivity Response | 2 | accepted | EID1235A siRNA screen identified BAP1 associated with HDAC1 and HDAC2 expression. HDAC2 or BAP1 depletion sensitized a mesothelioma cell line (MSTO-211H) to HDAC inhibitors vorinostat or mocetinostat. The pa… (full text at CIViC) PMID 25970771 · Sacco et al., 2015 · Open in CIViC | civic |
| Olaparib | Kidney CarcinomaALIAS | |||||||
| BAP1 Mutation8 | ||||||||
| (prognostic) | Clear Cell Renal Cell Carcinoma | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID459In patients with clear cell renal cell carcinoma, in a multivariate analysis those with mutations in BAP1 had worse overall survival than wild-type. PMID 23797736 · Sato et al., 2013 · Open in CIViC | civic |
| 〃 | Renal Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 5 | accepted | EID460In patients with clear cell renal cell carcinoma, in a multivariate analysis those with mutations in BAP1 had worse overall survival than wild-type. PMID 23797736 · Sato et al., 2013 · Open in CIViC | civic |
| 〃 | Clear Cell Renal Cell Carcinoma | Prognostic | B | Supports Poor Outcome | 5 | accepted | ||
| BAP1 Mutation + NF2 Mutation + SETD2 MutationBAP1SETD2NF21 | ||||||||
| Samotolisib | Malignant Mesothelioma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID11742In this study, 42 patients with malignant pleural or peritoneal mesothelioma were treated with single-agent LY3023414 (Samotolisib). Among the 42 patients, 11 had BAP1 mutations, while SETD2 and NF2 m… (full text at CIViC) PMID 33660194 · Zauderer et al., 2021 · Open in CIViC | civic |
Data updated 13 hours 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.
| GlioblastomaCURATED_BROADER |
| Predictive |
| D |
| Supports Sensitivity Response |
| 2 |
| submitted |
EID10938ATRX deficient glioblastoma model cell lines were created using CRISPR-based gene editing to knock-out ATRX in immortalized astrocytes. The ATRX knock-out cells were found to be particularly sensitive… (full text at CIViC) PMID 34118569 · Garbarino et al., 2021 · Open in CIViC |
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| Predictive |
| B |
| Supports Sensitivity Response |
| 3 |
| accepted |
EID1647A retrospective tumor sample study found that the loss of ATRX expression (less than 10% of nuclei) in IDH-mutant astrocytomas treated with temozolomide or a combination of procarbazine, lomustine and… (full text at CIViC) PMID 23904111 · Wiestler et al., 2013 · Open in CIViC |
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| AZ20 + VE-821Substitutes | Osteosarcoma | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID5832Loss of the chromatin-remodeling protein ATRX associates with ALT in cancers. Inhibition of the protein kinase ATR, a critical regulator of recombination recruited by RPA, disrupts ALT and triggers ch… (full text at CIViC) PMID 25593184 · Flynn et al., 2015 · Open in CIViC | civic |
| Cervical AdenocarcinomaCURATED_BROADER |
| Predictive |
| D |
| Supports Resistance |
| 3 |
| accepted |
EID457In the cervial andenocarcinoma cell line HeLa, when AURK-A was overexpressed, the cells were resistant to the apoptotic effects of Taxol. PMID 12559175 · Anand et al., 2003 · Open in CIViC |
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| Platinum Compound | Ovarian Serous AdenocarcinomaALIAS | Predictive | B | Supports Resistance | 3 | accepted | EID1650A study of 41 patients with high-grade ovarian serous carcinoma found that high expression levels of AURKA correlated with poorer overall survival (P = 0.001; HR 0.14) and platinum therapy resistance … (full text at CIViC) PMID 27209210 · Mignogna et al., 2016 · Open in CIViC | civic |
| Predictive |
| D |
| Supports Sensitivity Response |
| 3 |
| submitted |
EID5930BAP1 loss sensitized cells to the PARP inhibitor olaparib. In addition, BAP1-deficient cells were more sensitive to ionizing radiation. PMID 22683710 · Peña-Llopis et al., 2012 · Open in CIViC |
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EID461In patients with clear cell renal cell carcinoma, those with nonsilent mutations of BAP1 had worse overall survival than wild-type. PMID 23792563 · 2013, Nature · Open in CIViC |
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| CDK4/6 Inhibition | Pleural Malignant MesotheliomaALIAS | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID12008The effect of CDK4/6 inhibitors (abemaciclib or palbociclib) was tested in patient-derived malignant pleural mesothelioma (MLM) cell lines. Of the three patient-derived cell lines, two of the cell lin… (full text at CIViC) PMID 34588615 · Aliagas et al., 2021 · Open in CIViC | civic |
| Everolimus + SunitinibSequential | Clear Cell Renal Cell Carcinoma | Predictive | B | Supports Resistance | 4 | accepted | EID5339This study evaluated the effects of everolimus and sunitinib on patients with metastatic renal cell carcinoma. A total of 220 patients with RCC were evaluated for 341 genes at 540x coverage. Of all 22… (full text at CIViC) PMID 27751729 · Hsieh et al., 2017 · Open in CIViC | civic |
| Olaparib | Malignant Mesothelioma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID11740In this study, 23 patients with refractory mesothelioma harbouring germline or somatic BAP1 mutations were treated with olaparib. The median PFS was 3.6 months (95% CI, 2.7-4.2), and the median OS was… (full text at CIViC) PMID 34661178 · Ghafoor et al., 2021 · Open in CIViC | civic |
| 〃 | Malignant Mesothelioma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID11741In this study, 23 patients with refractory mesothelioma harbouring germline or somatic BAP1 mutations were treated with olaparib. The median PFS was 3.6 months (95% CI, 2.7-4.2), and the median OS was… (full text at CIViC) PMID 34661178 · Ghafoor et al., 2021 · Open in CIViC | civic |
| Panobinostat + Trichostatin A + Valproic Acid + VorinostatSubstitutes | Uveal Melanoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1234Somatic and germline BAP1 mutations are associated with uveal melanoma. In this preclinical study, gene set enrichment analysis revealed HDAC inhibitors as potential drugs in BAP1 mutant uveal melanom… (full text at CIViC) PMID 22038994 · Landreville et al., 2012 · Open in CIViC | civic |