Cancer
Neoplasm of Uncertain Histogenesis
CI-CAN-00000034Explore in graph →
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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 |
|---|---|---|---|---|---|---|---|---|
| BCL2 F104L1 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Predictive | B | Supports Resistance | 3 | submitted | EID8187Associated with venetoclax resistance in 2 high-risk CLL patients post ibrutinib in "progressive CLL" PMID 32232486 · Lucas et al., 2020 · Open in CIViC | civic |
| BCL2 F104S1 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Predictive | B | Supports Resistance | 3 | submitted | EID8186Associated with venetoclax resistance in high-risk CLL post ibrutinib in "progressive CLL" PMID 32232486 · Lucas et al., 2020 · Open in CIViC | civic |
| BCL2 G101A1 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Predictive | B | Supports Resistance | 4 | submitted | EID8184Associated with venetoclax resistance in high-risk CLL post ibrutinib in "progressive CLL" PMID 32232486 · Lucas et al., 2020 · Open in CIViC | civic |
| BCL2 G101V7 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia | Predictive | B | Supports Resistance | 4 | submitted | EID8174This study identified G101V mutation in BCL2 emerged in 7 out of 15 patients with CLL progression treated with Venetoclax. In addition, this study demonstrated that the G101V mutation impairs binding … (full text at CIViC) PMID 30514704 · Blombery et al., 2019 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Predictive | C | Supports Resistance | 4 | submitted | EID7970Four of six heavily pretreated, high-risk CLL patients with a 17p deletion from the phase 2 trial M13-9824 with continuous venetoclax treatment, who were treated with venetoclax for a period longer th… (full text at CIViC) PMID 31004028 · Tausch et al., 2019 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Predictive | C | Supports Resistance | ||||
| BCL2 L119V1 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Predictive | B | Supports Resistance | 3 | submitted | EID8190Associated with venetoclax resistance in high-risk CLL post ibrutinib in "progressive CLL" PMID 32232486 · Lucas et al., 2020 · Open in CIViC | civic |
| BCL2L11 Alternative splicing1 | ||||||||
| Imatinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | D | Supports Resistance | 4 | submitted | EID9699Primary imatinib resistance is caused by a deletion polymorphism in intron 2 (see EID 1280 and 1281). An in vitro study shows that the deletion biases BIM splicing from exon 4 to exon 3. Adding ASOs t… (full text at CIViC) PMID 29100409 · Liu et al., 2017 · Open in CIViC | civic |
| BCL2L11 Deletion Polymorphism3 | ||||||||
| Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID1281The BIM (BCL2L11) deletion polymorphism was identified in an EGFR Mutant NSCLC cell line with resistance to EGFR-TKI (HCC2779). Introduction of this polymorphism in a previously EGFR-inhibitor sensiti… (full text at CIViC) PMID 22426421 · Ng et al., 2012 · Open in CIViC | civic |
| Imatinib | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Predictive | B | Supports Resistance | 4 | accepted | EID1280DNA sequencing was performed in five Ph+ CML samples with sensitivity or resistance to imatinib. A structural variation in BIM2 (BCL2L11) with an identical 2,903-bp genomic deletion was identified in … (full text at CIViC) PMID 22426421 · Ng et al., 2012 · Open in CIViC | civic |
| 〃 | ||||||||
| BCL2 Mutation1 | ||||||||
| (prognostic) | Follicular Lymphoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID5992In a multivariate analysis, BCL2 mutations and high FL international prognostic index were independent risk factors for transformation and death due to lymphoma. Some mutant Bcl-2 proteins exhibited e… (full text at CIViC) PMID 25452615 · Correia et al., 2015 · Open in CIViC | civic |
| BCL2 Overexpression3 | ||||||||
| (prognostic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID423In patients with Diffuse Large B-Cell Lymphoma, those with increased levels of BCL2 were shown to have decreased overall, disease-free, and relapse-free survival. PMID 9207459 · Gascoyne et al., 1997 · Open in CIViC | civic |
| 〃 | Diffuse Large B-Cell LymphomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | rejected | EID424In patients with Diffuse Large B-Cell Lymphoma, those with increased levels of BCL2 were shown to have decreased OS, DFS, and RFS. PMID 9207459 · Gascoyne et al., 1997 · Open in CIViC | civic |
| Dinaciclib + VenetoclaxCombination | Lymphoma | Predictive | D | |||||
| BCL2 R107_R110dup2 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia | Predictive | B | Supports Resistance | 4 | submitted | EID8309This study is a follow-up report after the original publication (PMID 30514704). R107_R110dup mutation was identified in combination with other BCL2 mutations including G101V in 5 CLL patients with ve… (full text at CIViC) PMID 31951646 · Blombery et al., 2020 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Predictive | B | Supports Resistance | 3 | submitted | EID8188Associated with venetoclax resistance in high-risk CLL patients post ibrutinib in 2 cases of "progressive CLL" and 1 case of Richter transformation PMID 32232486 · Lucas et al., 2020 · Open in CIViC | civic |
| BCL2 R129L1 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia | Predictive | C | Supports Resistance | 3 | submitted | EID8307This study is a follow-up report after the original publication (PMID 30514704). R129L mutation was identified in combination with other BCL2 mutations including G101V in 2 CLL patients with venetocla… (full text at CIViC) PMID 31951646 · Blombery et al., 2020 · Open in CIViC | civic |
| BCL2 reg_e@[IGH]::BCL22 | ||||||||
| (diagnostic) | Follicular Lymphoma | Diagnostic | B | Supports Positive | 5 | submitted | EID11808This translocation is a hallmark feature of follicular lymphoma. Although it is not present in every case, it is one of the most common genetic features of FL. FISH or IHC staining for BCL2 is part of… (full text at CIViC) PMID 3537802 · Yunis et al., 1987 · Open in CIViC | civic |
| 〃 | Diffuse Large B-Cell LymphomaCURATED_BROADER | Diagnostic | B | Supports Positive | 4 | accepted | EID407The t(14;18) transloaction of BCL2 is shown to be associated with germinal-center B-cell–like diffuse large-B-cell lymphomas. PMID 12075054 · Rosenwald et al., 2002 · Open in CIViC | civic |
| BCL2 Translocation1 | ||||||||
| (diagnostic) | High Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements | Diagnostic | A | Supports Positive | 4 | submitted | EID11810The combination of these genetic features are diagnostic for this newly defined entity as per the latest ICC and WHO guidelines PMID 35653592 · Campo et al., 2022 · Open in CIViC | civic |
| BCL2 V156D1 | ||||||||
| Venetoclax | Chronic Lymphocytic Leukemia | Predictive | B | Supports Resistance | 4 | submitted | EID8306This study is a follow-up report after the original publication (PMID 30514704). V156D mutation was identified in combination with other BCL2 mutations including G101V in 6 CLL patients with venetocla… (full text at CIViC) PMID 31951646 · Blombery et al., 2020 · Open in CIViC | civic |
| BCL6 Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11915This 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 |
| BCL7A mutation2 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 4 | submitted | EID11936This study reportedly sequenced 1001 DLBCL tumors using whole exome sequencing. They reported 150 recurrently mutated genes. Only genes that have been confirmed by other similar studies were added to … (full text at CIViC) PMID 28985567 · Reddy et al., 2017 · Open in CIViC | civic |
| 〃 | Burkitt Lymphoma | Oncogenic | E | Supports Oncogenicity | 3 | submitted | EID11816Mutations in this gene have been described in several studies including the one referenced here. PMID 30617194 · Grande et al., 2019 · Open in CIViC | civic |
| CCNB3 Fusion6 | ||||||||
| (diagnostic) | Sarcoma with BCOR Genetic Alterations | Diagnostic | B | Supports Positive | 4 | accepted | EID9011This study consists of a cohort of 42 pediatric and adult patients with sarcomas that were classified as undifferentiated. Six of the forty two patients had BCOR::CCNB3 fusions detected by whole trans… (full text at CIViC) PMID 25360585 · Peters et al., 2015 · Open in CIViC | civic |
| 〃 | Sarcoma with BCOR Genetic Alterations | Diagnostic | B | Supports Positive | 3 | accepted | EID10111Kao, et al. (2018) presented 36 BCOR::CCNB3 sarcoma cases (86% were males; mean and median age at presentation was 15 years (range from 2 to 44 years); 78% showed mainly primitive round cells morpholo… (full text at CIViC) PMID 29300189 · Kao et al., 2018 · Open in CIViC | civic |
| 〃 | Sarcoma with BCOR Genetic Alterations | Diagnostic | B | Supports Positive | ||||
| CCNB3 Fusion + MAML3 FusionCCNB3MAML31 | ||||||||
| (diagnostic) | Sarcoma with BCOR Genetic Alterations | Diagnostic | B | Supports Positive | 3 | accepted | EID11590BCOR expression was evaluated in a cohort of 25 small blue round cell tumors (SBRCTs) with BCOR fusions (BCOR::MAML3, BCOR::CCNB3), BCOR exon 15 ITDs, or YWHAE-NUTM2B fusion (which is known to upregul… (full text at CIViC) PMID 27428733 · Kao et al., 2016 · Open in CIViC | civic |
| BCOR ITD11 | ||||||||
| (diagnostic) | Clear Cell Sarcoma of the KidneyALIAS | Diagnostic | B | Supports Positive | 5 | accepted | EID10801BCOR internal tandem duplications (ITDs) were found frequently in cases of clear cell sarcoma of kidney (CCSK), a rare pediatric renal cancer. The study initially evaluated 3 CCSK samples by whole exo… (full text at CIViC) PMID 26573325 · Roy et al., 2015 · Open in CIViC | civic |
| 〃 | Central Nervous System Tumor with BCOR Internal Tandem Duplication | Diagnostic | B | Supports Positive | 4 | accepted | EID10800The authors generated genome-wide DNA methylation profiles of 323 tumors with an institutional diagnosis of ‘primitive neuroectodermal tumors of the central nervous system (CNS-PNETs)’, which are hi… (full text at CIViC) PMID 26919435 · Sturm et al., 2016 · Open in CIViC | civic |
| (oncogenic) | Clear Cell Sarcoma of the KidneyALIAS | |||||||
| BCOR Mutation2 | ||||||||
| (prognostic) | Myelodysplastic SyndromeCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID7450Multivariate analysis on 354 MDS patients including age, International Prognostic Scoring System, transfusion dependency, and mutational status confirmed a significant inferior OS to patients with a B… (full text at CIViC) PMID 24047651 · Damm et al., 2013 · Open in CIViC | civic |
| 〃 | Malignant Gastric Neoplasm | Prognostic | B | Supports Better Outcome | 3 | accepted | EID168146 patients with poorly cohesive, signet-cell ring, gastric carcinoma were evaluated for genetic mutations. Overall survival rate of BCOR positive cases were significantly better than BCOR negative c… (full text at CIViC) PMID 27313181 · Rokutan et al., 2016 · Open in CIViC | civic |
| ABL1 Fusion1 | ||||||||
| (diagnostic) | Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS | Diagnostic | A | Supports Positive | 4 | accepted | EID220In this 2010 review, the authors highlighted the central diagnostic and pathogenic role of the BCR::ABL1 fusion gene in Chronic Myeloid Leukemia (CML), emphasizing that its presence is the characteriz… (full text at CIViC) PMID 20537386 · An et al., 2010 · 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.
| 4 |
| submitted |
EID8305This study is a follow-up report after the original publication (PMID 30514704). The authors described multiple acquired resistance mutations including G101V in BCL-2 that occur in different CLL cells… (full text at CIViC) PMID 31951646 · Blombery et al., 2020 · Open in CIViC |
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| 〃 | Chronic Lymphocytic Leukemia | Predictive | C | Does Not Support Resistance | 3 | submitted | EID8303Previous work by this group used WES and was unable to identify BCL2 G101V mutation in 9 CLL patients with resistance to venetoclax (PMID 29463802). Based on Tausch et al work (PMID 31004028), this gr… (full text at CIViC) PMID 31666345 · Weiss et al., 2019 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Predictive | C | Supports Resistance | 2 | accepted | EID8185The effective cohort in this study was 11 CLL patients who were first treated with ibrutinib and then on progression treated with venetoclax until progression. Patient samples were sequenced before an… (full text at CIViC) PMID 32232486 · Lucas et al., 2020 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Predictive | D | Supports Resistance | 3 | submitted | EID8334This study demonstrated that the G101V mutation impairs binding of venetoclax to BCL2, confers resistance to venetoclax in both patient leukemia cells and engineered cell lines, thus provides a select… (full text at CIViC) PMID 30514704 · Blombery et al., 2019 · Open in CIViC | civic |
| 〃 | Chronic Lymphocytic Leukemia | Predictive | D | Supports Resistance | 3 | accepted | EID8841This study described the similar crystal structures of BCL-2 wild-type and G101V when bound to venetoclax. Steady state competition surface plasmon resonance experiments demonstrated a ~177 fold decre… (full text at CIViC) PMID 31160589 · Birkinshaw et al., 2019 · Open in CIViC | civic |
| Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS |
| Predictive |
| B |
| Supports Sensitivity Response |
| 4 |
| submitted |
EID9701In a clinical study including 200 patients, deletion polymorphism is not significantly associated with resistance to imatinib (p = 0.116). PMID 25295932 · Chen et al., 2014 · Open in CIViC |
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| Supports Resistance |
| 2 |
| submitted |
EID9313Within a preclinical study, the efficacy of Dinaciclib and ABT-199 in MYC-BCL2 double expressing lymphoma (DLBCL) was investigated through mouse models and DLBCL cell lines. Overexpressing DLBCL BCL2 … (full text at CIViC) PMID 25882699 · Li et al., 2015 · Open in CIViC |
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| 3 |
| accepted |
EID12568In this 2017 study reviewing 753 sarcoma cases, 11 tumors with the BCOR::CCNB3 fusion were identified using immunohistochemistry and RT-PCR. These tumors were found exclusively in males, with a mean a… (full text at CIViC) PMID 28420319 · Ludwig et al., 2017 · Open in CIViC |
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| 〃 | Clear Cell Sarcoma of the KidneyALIAS | Diagnostic | C | Supports Positive | 2 | accepted | EID12003In this 2018 study, the authors aimed to identify driver events in 'double negative' clear cell sarcoma of the kidney (CCSK) where neither BCOR ITDs nor the YWHAE::NUTM2 gene fusion are detected. Elev… (full text at CIViC) PMID 28833375 · Wong et al., 2018 · Open in CIViC | civic |
| 〃 | Clear Cell Sarcoma of the KidneyALIAS | Diagnostic | C | Supports Positive | 2 | accepted | EID12004In this 2020 study, the authors report two patients with BCOR::CCNB3 fusion-positive clear cell sarcoma of the kidney (CCSK). Cases were males aged 10 and 14 years who presented with advanced disease.… (full text at CIViC) PMID 31876361 · Han et al., 2020 · Open in CIViC | civic |
| 〃 | Clear Cell Sarcoma of the KidneyALIAS | Diagnostic | C | Supports Positive | 2 | accepted | EID12005In this 2017 study, the authors describe two primary renal sarcomas harboring BCOR::CCNB3 gene fusions and compare the morphological and immunochemical features to typical clear cell sarcoma of the ki… (full text at CIViC) PMID 28817404 · Argani et al., 2017 · Open in CIViC | civic |
| Oncogenic |
| B |
| Supports Oncogenicity |
| 4 |
| accepted |
EID1080227 cases of CCSK were profiled by whole exome sequencing and whole transcriptomics, identifying BCOR ITDs in the majority (23/27, 85%). BCOR encodes a key constituent of a variant polycomb repressive… (full text at CIViC) PMID 26573325 · Roy et al., 2015 · Open in CIViC |
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| 〃 | Central Nervous System Tumor with BCOR Internal Tandem Duplication | Oncogenic | B | Supports Oncogenicity | 4 | accepted | EID1080410/323 studied high-grade primitive neuroectodermal tumors of the central nervous system (CNS-HGPNETs) clustered together based on their unique methylation profile. 10/10 of those tumors exhibited in… (full text at CIViC) PMID 26919435 · Sturm et al., 2016 · Open in CIViC | civic |
| (diagnostic) | Clear Cell Sarcoma of the KidneyALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID11423High BCOR expression which was associated with an internal tandem duplication (ITD) of 89 to 144 bp in exon 16 of the BCOR gene was identified in 20 of 20 (100%) of cases of clear cell sarcoma of the … (full text at CIViC) PMID 26098867 · Ueno-Yokohata et al., 2015 · Open in CIViC | civic |
| 〃 | Sarcoma | Diagnostic | B | Supports Positive | 4 | submitted | EID11524Twenty nine cases of infantile sarcoma cases, including 22 cases of soft tissue undifferentiated round cell sarcoma (URCS) and 7 cases of primitive myxoid mesenchymal tumour, were profiled using RNA s… (full text at CIViC) PMID 26945340 · Kao et al., 2016 · Open in CIViC | civic |
| 〃 | Sarcoma | Diagnostic | B | Supports Positive | 4 | submitted | EID11525Thirty three cases of undifferentiated round cell sarcoma with either BCOR internal tandem duplication or YWHAE fusions were reviewed in this cohort, comprising 31 infants and two adolescents. Of the … (full text at CIViC) PMID 32372022 · Antonescu et al., 2020 · Open in CIViC | civic |
| 〃 | Central Nervous System Tumor with BCOR Internal Tandem Duplication | Diagnostic | B | Supports Positive | 3 | accepted | EID1088710 cases of high-grade neuroepithelial tumor (HGNET) with BCOR exon 15 ITD were studied. In addition, 25 previously reported and published patients were included in survival analyses. These tumors ar… (full text at CIViC) PMID 31104347 · Ferris et al., 2020 · Open in CIViC | civic |
| 〃 | Clear Cell Sarcoma of the KidneyALIAS | Diagnostic | B | Supports Positive | 3 | accepted | EID11424Whole transcriptome sequencing on tumors from 8 patients with clear cell sarcoma of the kidney identified BCOR ITD and overexpression of BCOR in all samples. The BCOR ITD was confirmed on tumor DNA.… (full text at CIViC) PMID 26516930 · Astolfi et al., 2015 · Open in CIViC | civic |
| 〃 | Central Nervous System Tumor with BCOR Internal Tandem Duplication | Diagnostic | B | Supports Positive | 3 | accepted | EID11581Six cases of CNS high-grade neuroepithelial tumor (HGNET) with BCOR exon 15 internal tandem duplication (ITD) were studied. The authors analyzed their clinical, pathologic and molecular characteristic… (full text at CIViC) PMID 29226988 · Yoshida et al., 2018 · Open in CIViC | civic |
| 〃 | Sarcoma | Diagnostic | B | Supports Positive | 3 | accepted | EID11589BCOR expression was evaluated in a cohort of 25 small blue round cell tumors (SBRCTs) with BCOR fusions (BCOR::MAML3, BCOR::CCNB3), BCOR exon 15 ITDs, or YWHAE-NUTM2B fusion (which is known to upregul… (full text at CIViC) PMID 27428733 · Kao et al., 2016 · Open in CIViC | civic |