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Variants & evidence
322 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 |
|---|---|---|---|---|---|---|---|---|
| KRAS G12S4 | ||||||||
| Melphalan | Multiple Myeloma | Predictive | B | Supports Resistance | — | submitted | EID2276Activating mutations in KRAS or NRAS were observed more frequently in multiple myeloma patients than in patients with monoclonal gammopathy of uncertain significance (MGUS) (31% vs. 5% ). Another stu… (full text at CIViC) PMID 15339850 · Rasmussen et al., 2005 · Open in CIViC | civic |
| 〃 | Multiple Myeloma | Predictive | D | Supports Resistance | 2 | accepted | EID2277In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 11050000 · Rowley et al., 2000 · Open in CIViC | civic |
| 〃 | Multiple Myeloma | Predictive | D | Supports Resistance | 2 | accepted | EID2278In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 12483530 · Rowley et al., 2002 · Open in CIViC | civic |
| 〃 | Multiple Myeloma | Predictive | D | Supports Resistance | 2 | accepted | EID2279In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 16497971 · Hoang et al., 2006 · Open in CIViC | civic |
| KRAS G131 | ||||||||
| (prognostic) | Multiple Myeloma | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID488In a retrospective study of 439 patients with multiple myeloma enrolled in a clinical trial, 28 had mutations in KRAS (22/28 in G12/G13). Those with KRAS (but not NRAS) mutations had worse overall (me… (full text at CIViC) PMID 18528420 · Chng et al., 2008 · Open in CIViC | civic |
| KRAS Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11960This study performed exome sequencing on 55 DLBCL tumor samples and identified several significantly mutated genes including KRAS. PMID 22343534 · Lohr et al., 2012 · Open in CIViC | civic |
| KRAS Q611 | ||||||||
| (prognostic) | Multiple Myeloma | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID489In a retrospective study of 439 patients with multiple myeloma enrolled in a clinical trial, 28 had mutaions in KRAS. Those with mutations had worse overall and progression free survival than those wi… (full text at CIViC) PMID 18528420 · Chng et al., 2008 · Open in CIViC | civic |
| LTB Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11961The authors analyzed 304 primary DLBCLs using whole exome sequencing and targeted sequencing. This one one of the genes they identified as significantly enriched for somatic mutations. PMID 29713087 · Chapuy et al., 2018 · Open in CIViC | civic |
| LYN Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 2 | submitted | EID11962The authors analyzed 304 primary DLBCLs using whole exome sequencing and targeted sequencing. This one one of the genes they identified as significantly enriched for somatic mutations. The rate of mut… (full text at CIViC) PMID 29713087 · Chapuy et al., 2018 · Open in CIViC | civic |
| MCL1 Amplification1 | ||||||||
| Mcl-1 Inhibitor MIK665 | Multiple Myeloma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11768In this preclinical study, the sensitivity of Multiple Myeloma tumors harboring 1q21 amplification to MCL-1 inhibitor S63845 was tested. The effect of the MCL-1 inhibitor was tested in 21 human myelom… (full text at CIViC) PMID 31856269 · Slomp et al., 2019 · Open in CIViC | civic |
| MEF2B mutation2 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11919Multiple studies have demonstrated an enrichment for somatic missense mutations in MEF2B including multiple hot spots. PMID 21796119 · Morin et al., 2011 · Open in CIViC | civic |
| 〃 | Mantle Cell Lymphoma | Oncogenic | E | Supports Oncogenicity | 3 | submitted | EID11872[the study] identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the … (full text at CIViC) PMID 24145436 · Beà et al., 2013 · Open in CIViC | civic |
| MEF2C Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11963The authors analyzed 304 primary DLBCLs using whole exome sequencing and targeted sequencing. This one one of the genes they identified as significantly enriched for somatic mutations. PMID 29713087 · Chapuy et al., 2018 · Open in CIViC | civic |
| MGA Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 3 | submitted | EID11964This study sequenced 73 DLBCL tumors (34 with matched constitutional DNA) and reported 322 genes they deemed recurrently mutated. Only genes that have been confirmed by other similar studies were adde… (full text at CIViC) PMID 23292937 · Zhang et al., 2013 · Open in CIViC | civic |
| MPEG1 Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11965The authors performed an integrative analysis of genomes, exomes and transcriptome data from DLBCL and identified recurrent coding and non-coding loci that are commonly mutated in DLBCL PMID 30275490 · Arthur et al., 2018 · Open in CIViC | civic |
| MS4A1 Mutation1 | ||||||||
| R-CHOP Regimen | Diffuse Large B-Cell LymphomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID10367A targeted sequencing study of 135 relapsed/refractory DLBCL patients identified an association between missense mutations in MS4A1 and acquired resistance to R-CHOP. PMID 32589730 · Rushton et al., 2020 · Open in CIViC | civic |
| MYCL EXPRESSION1 | ||||||||
| I-BET151 + JQ1Substitutes | Multiple Myeloma | Predictive | D | Supports Sensitivity Response | 1 | accepted | EID1706Four myeloma cell lines were treated with two different BET inhibitors (I-BET151 or JQ1). Proliferation of three cell lines (KMS11, RPMI8226 and MM1S) but not U266 (only partial inhibition) was strong… (full text at CIViC) PMID 27276402 · Suzuki et al., 2016 · Open in CIViC | civic |
| MYC Overexpression1 | ||||||||
| JQ-1 | Multiple Myeloma | Predictive | D | Supports Sensitivity Response | 5 | accepted | EID5505BET inhibition by JQ1 downregulates MYC transcription, followed by genome-wide downregulation of Myc-dependent target genes. In experimental models of multiple myeloma, a Myc-dependent hematologic mal… (full text at CIViC) PMID 21889194 · Delmore et al., 2011 · Open in CIViC | civic |
| MYC Translocation1 | ||||||||
| (diagnostic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Diagnostic | A | Supports Positive | 4 | submitted | EID11809MYC translocations, often (but not always) involving immunoglobulin loci, are common in DLBCL and one of two defining features of high-grade B-cell lymphoma with MYC and BCL2 rearrangements PMID 35653592 · Campo et al., 2022 · Open in CIViC | civic |
| BCL2 Translocation + MYC TranslocationMYCBCL21 | ||||||||
| (diagnostic) | High Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements | Diagnostic | A | Supports Positive | 4 | submitted | EID11811MYC and BCL2 rearrangements together are defining diagnostic features of this new entity PMID 35653592 · Campo et al., 2022 · Open in CIViC | civic |
| BCL2 Translocation + BCL6 Translocation + MYC TranslocationMYCBCL2BCL61 | ||||||||
| (prognostic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Prognostic | C | Supports Poor Outcome | 2 | submitted | EID9813In 2016 the WHO added a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with MYC AND [BCL2 OR BCL6] translocations. These represent less than 1… (full text at CIViC) PMID 28600333 · Friedberg, 2017 · Open in CIViC | civic |
| MYD88 L265P3 | ||||||||
| (prognostic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID9376A meta-analysis of 40 published studies on 2736 DLBCL patients. The MYD88 L265P mutation was significantly associated with old age and poor overall survival, but not with sex and clinical stage. This … (full text at CIViC) PMID 28496180 · Lee et al., 2017 · Open in CIViC | civic |
| Ibrutinib | Lymphoplasmacytic Lymphoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID986A prospective study of ibrutinib in 63 symptomatic patients with Waldenström's macroglobulinemia who had received at least one previous treatment. The response rates were highest among patients with M… (full text at CIViC) PMID 25853747 · Treon et al., 2015 · Open in CIViC | civic |
| IMG-2005-5 + IRAK-1/4 InhibitorSubstitutes | Lymphoplasmacytic Lymphoma | |||||||
| NFKBIA Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11967This gene was identified as recurrently mutated in an analysis of 574 DLBCL exomes PMID 29641966 · Schmitz et al., 2018 · Open in CIViC | civic |
| NFKBIE Mutation2 | ||||||||
| (oncogenic) | Mantle Cell Lymphoma | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11904Through a meta-analysis of exome and whole genome sequencing data, this study identified 18 genes that were significantly enriched for mutations in MCL including NFKBIE. PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC | civic |
| 〃 | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11966This gene was identified as recurrently mutated in an analysis of 574 DLBCL exomes PMID 29641966 · Schmitz et al., 2018 · Open in CIViC | civic |
| NFKBIZ 3-prime UTR mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11968The authors performed an integrative analysis of genomes, exomes and transcriptome data from DLBCL and identified recurrent coding and non-coding loci that are commonly mutated in DLBCL PMID 30275490 · Arthur et al., 2018 · Open in CIViC | civic |
| NOL9 Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11969The authors performed an integrative analysis of genomes, exomes and transcriptome data from DLBCL and identified recurrent coding and non-coding loci that are commonly mutated in DLBCL PMID 29641966 · Schmitz et al., 2018 · Open in CIViC | civic |
| NOTCH1 L1678P1 | ||||||||
| Nirogacestat | Adult T-Cell Leukemia/Lymphoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID5921Genetic evaluation of a single patient with a complete response in a phase 1 trial of PF-03084014 revealed the presence of a known activating NOTCH1 mutation, L1678P. PMID 26407235 · Papayannidis et al., 2015 · Open in CIViC | civic |
| NOTCH1 Mutation4 | ||||||||
| (prognostic) | Mantle Cell Lymphoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID49414 out of 121 patient samples contained mutations in NOTCH1. Those with mutations had worse overall survival than wild-type (median OS, 1.43 years vs. 3.86 years). PMID 22210878 · Kridel et al., 2012 · Open in CIViC | civic |
| 〃 | Mantle Cell Lymphoma | Prognostic | E | Supports Poor Outcome | 4 | submitted | EID11895This study confirmed clinical associations between TP53 and NOTCH1 with poor outcome. PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC | civic |
| (oncogenic) | Mantle Cell Lymphoma | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11900Through a meta-analysis of exome and whole genome sequencing data, this study identified 18 genes that were significantly enriched for mutations in MCL including NOTCH1. | |
| NOTCH2 Mutation2 | ||||||||
| (oncogenic) | Mantle Cell Lymphoma | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11902Through a meta-analysis of exome and whole genome sequencing data, this study identified 18 genes that were significantly enriched for mutations in MCL including NOTCH2. PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC | civic |
| 〃 | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11971This gene was identified as recurrently mutated in an analysis of 574 DLBCL exomes PMID 29641966 · Schmitz et al., 2018 · Open in CIViC | civic |
| ALK Fusion2 | ||||||||
| Crizotinib | Anaplastic Large Cell Lymphoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1241In the second part of this Phase I study NCT00939770, nine patients between the ages of 12 months and 22 years with anaplastic large cell lymphoma (ALCL), who were refractory to treatment and for whom… (full text at CIViC) PMID 23598171 · Mossé et al., 2013 · Open in CIViC | civic |
| 〃 | Anaplastic Large Cell Lymphoma | Predictive | D | Supports Sensitivity Response | 5 | accepted | EID1239NPM-ALK in anaplastic large cell lymphoma (ALCL) was the first ALK-fusion to be discovered and characterized. In this study, targeted activity against NPM-ALK by the ALK and MET inhibitor crizotinib … (full text at CIViC) PMID 18089725 · Christensen et al., 2007 · Open in CIViC | civic |
| ALK I1171N + ALK Fusion1 | ||||||||
| Crizotinib | Anaplastic Large Cell Lymphoma | Predictive | D | Supports Resistance | 2 | submitted | EID4632In an in vitro study, cell lines expressing NPM-ALK I1171N, SUPM2CR03 (endogenous expression) and Ba/F3 (overexpression), demonstrated resistance to crizotinib treatment (IC50: 338 nmol/L and IC50: 21… (full text at CIViC) PMID 23239810 · Ceccon et al., 2013 · Open in CIViC | civic |
| ALK I1171S + ALK Fusion1 | ||||||||
| Crizotinib | Anaplastic Large Cell Lymphoma | Predictive | D | Supports Resistance | 3 | submitted | EID12653In an in vitro study, a FL5.12 cell line expressing NPM1-ALK (a known sensitizing alteration to crizotinib) and an ALK I1171S co-mutation, demonstrated resistance to crizotinib treatment (IC50: 345.03… (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC | civic |
| ALK T1151M + ALK Fusion1 | ||||||||
| Ceritinib | Anaplastic Large Cell Lymphoma | Predictive | D | Supports Resistance | 3 | submitted | EID12659In an in vitro study, a FL5.12 cell line expressing NPM1-ALK (a known sensitizing alteration to crizotinib) and an ALK T1151M co-mutation, demonstrated resistance to ceritinib treatment (IC50: 95.78 n… (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC | civic |
| NRAS Mutation1 | ||||||||
| (prognostic) | Multiple Myeloma | Prognostic | B | Supports N/A | 4 | accepted | EID496In patients with multiple myeloma, the presence of a mutation in NRAS was not significantly associated with progression-free or overall survival. PMID 18528420 · Chng et al., 2008 · Open in CIViC | civic |
| NSD2 Mutation1 | ||||||||
| (oncogenic) | Mantle Cell Lymphoma | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11898Through a meta-analysis of exome and whole genome sequencing data, this study identified 18 genes that were significantly enriched for mutations in MCL including WHSC1 (NSD2). PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC | civic |
| OSBPL10 Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11972This gene was identified as recurrently mutated in an analysis of 574 DLBCL exomes PMID 29641966 · Schmitz et al., 2018 · Open in CIViC | civic |
| P2RY8 mutation2 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11973This study performed exome sequencing on 55 DLBCL tumor samples and identified several significantly mutated genes including. PMID 22343534 · Lohr et al., 2012 · Open in CIViC | civic |
| 〃 | Burkitt Lymphoma | Oncogenic | E | Supports Oncogenicity | 3 | submitted | EID11834Mutations in this gene are common in BL according to several studies PMID 25274307 · Muppidi et al., 2014 · Open in CIViC | civic |
| PCBP1 mutation1 | ||||||||
| (oncogenic) | Burkitt Lymphoma | Oncogenic | E | Supports Oncogenicity | 3 | submitted | EID11833Described in several BL studies after this one PMID 26173642 · Wagener et al., 2015 · Open in CIViC | civic |
| PIM1 L2V1 | ||||||||
| Ibrutinib | Diffuse Large B-Cell Lymphoma Activated B-Cell Type | Predictive | D | Supports Resistance | 3 | accepted | EID9945Foundation panel results of baseline tumour samples from 48 patients with diffuse large B cell lymphoma identified PIM1 mutations in 6 patient samples, 5 of which were the DLBCL-ABC subtype. Four out … (full text at CIViC) PMID 27904766 · Kuo et al., 2016 · Open in CIViC | civic |
| PIM1 Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11974This is one of the first of many genes identified as targets of aberrant somatic hypermutation in DLBCL PMID 11460166 · Pasqualucci et al., 2001 · Open in CIViC | civic |
| PIM1 P81S1 | ||||||||
| Ibrutinib | Diffuse Large B-Cell Lymphoma Activated B-Cell Type | Predictive | D | Supports Resistance | 3 | accepted | EID9946Foundation panel results of baseline tumour samples from 48 patients with diffuse large B cell lymphoma identified PIM1 mutations in 6 patient samples, 5 of which were the DLBCL-ABC subtype. Four out … (full text at CIViC) PMID 27904766 · Kuo et al., 2016 · Open in CIViC | civic |
Data updated 21 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.
| D |
| Supports Sensitivity Response |
| 1 |
| accepted |
EID1641In a study of 30 patients with Waldenström’s macroglobulinemia, 87% had MYD88(L265P) mutations. Waldenstrom macroglobulinemia cells expressing MYD88(L265P) were treated with an MYD88 homodimerization… (full text at CIViC) PMID 22931316 · Treon et al., 2012 · Open in CIViC |
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PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC
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| 〃 | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11970This gene was identified as recurrently mutated in an analysis of 574 DLBCL exomes PMID 29641966 · Schmitz et al., 2018 · Open in CIViC | civic |