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BIOMARKER:

RAD51C mutation

i
Other names: RAD51C, RAD51 paralog C, R51H3, BROVCA3, RAD51L2
Entrez ID:
Related biomarkers:
1d
Synchronous lung and multiple soft tissue metastases developed from osteosarcoma of tibia: a rare case report and genetic profile analysis. (PubMed, BMC Musculoskelet Disord)
Osteosarcoma with extrapulmonary metastases is rare, especially located in the skeletal muscle, which predicts a worse clinical outcome compared with lung-only metastases. The several novel variants of ALK, BLM, PTCH1 in this patient might expand the mutational spectrums of the osteosarcoma. All the results may contribute to a better understanding of the clinical course and genetic characteristics of osteosarcoma patients with metastasis.
Journal
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ALK (Anaplastic lymphoma kinase) • RB1 (RB Transcriptional Corepressor 1) • PTCH1 (Patched 1) • MSH2 (MutS Homolog 2) • RAD51C (RAD51 paralog C)
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RB1 mutation • PTCH1 mutation • RAD51C mutation • BLM mutation
4d
New P2 trial • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
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BRCA1 mutation • BRCA2 mutation • HR positive • HER-2 negative • PALB2 mutation • RAD51D mutation • RAD51C mutation • HR positive + HER-2 negative • RAD51 mutation
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Keytruda (pembrolizumab) • Lynparza (olaparib)
8d
Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting
Clinical • Enrollment open
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EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • FGFR (Fibroblast Growth Factor Receptor) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
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Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
15d
LODESTAR: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes (clinicaltrials.gov)
P2, N=220, Recruiting, Clovis Oncology, Inc. | Trial completion date: May 2022 --> Mar 2023 | Trial primary completion date: Nov 2021 --> Dec 2022
Clinical • Trial completion date • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • FANCA (FA Complementation Group A) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • FANCA deletion • NBN mutation • RAD51 mutation
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Rubraca (rucaparib)
16d
Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
P2, N=57, Not yet recruiting, Memorial Sloan Kettering Cancer Center
Clinical • New P2 trial
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EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • FGFR (Fibroblast Growth Factor Receptor) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
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Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
29d
Niraparib for the Treatment of Leiomyosarcoma (clinicaltrials.gov)
P2, N=22, Not yet recruiting, Ohio State University Comprehensive Cancer Center
New P2 trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
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BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation
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Zejula (niraparib)
1m
Characteristics of Germline Non-BRCA Mutation Status of High-Risk Breast Cancer Patients in China and Correlation with High-Risk Factors and Multigene Testing Suggestions. (PubMed, Front Genet)
Family history showed a correlation with both BRCA (p = 0.005) and non-BRCA HRR gene mutation status (p = 0.036), so we strongly suggest that breast cancer patients with a BRCA-related family history receive comprehensive gene mutation testing in China, especially HRR genes, which are not only related to high risk of breast cancer, but also potentially related to poly ADP ribose polymerase inhibitor (PARPi) targeted therapy. The exact relationship of rare gene mutations to breast cancer predisposition and the pathogenicity of VUS need to be further investigated.
Clinical • Journal • BRCA Biomarker • PARP Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • HOXB13 (Homeobox B13) • ERCC3
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BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • BARD1 mutation • RAD54L mutation
2ms
Local features of penetrant mutations incidence in patients with prostate cancer in Republic of Bashkortostan (EMUC 2021)
The frequency of mutations in repair gene is characterized by territorial features. The frequency of determining pathogenic mutations in the genes in question was determined.
Clinical • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation
2ms
Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO (clinicaltrials.gov)
P2, N=89, Not yet recruiting, Institut fuer Frauengesundheit | Trial completion date: Oct 2025 --> Feb 2026 | Initiation date: Sep 2021 --> Jan 2022 | Trial primary completion date: Sep 2023 --> Jan 2024
Clinical • Trial completion date • Trial initiation date • Trial primary completion date
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HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
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BRCA1 mutation • BRCA2 mutation • HER-2 amplification • HER-2 negative • ATM mutation • HRD • PALB2 mutation • ER positive + PGR positive • PGR positive • RAD51D mutation • CHEK2 mutation • RAD51C mutation • BARD1 mutation • RAD51 mutation
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Keytruda (pembrolizumab) • Lynparza (olaparib)
2ms
New trial
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • HOXB13 (Homeobox B13) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • PMS2 mutation • NBN mutation
3ms
Clinical • New trial • Circulating tumor DNA
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression
3ms
Germline BRCA 1/2 and other predisposition genes in high-risk early-stage HR+/HER2- breast cancer (BC) patients treated with endocrine therapy (ET) with or without palbociclib: A secondary analysis from the PENELOPE-B study (SABCS 2021)
In this case-cohort analysis of 442 patients enrolled in the PENELOPE-B trial, the detection of BC predisposition genes was lower than expected with 10%. This is probably due to the low rate of g BRCA 1/2 carriers (3.4%), which could be influenced by the selection criteria of the trial. Patients with g BRCA 1/2 or other BC disposition genes had a comparable outcome to non-carriers in the PENELOPE-B trial.
Clinical • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • FANCM (FA Complementation Group M) • XRCC2 (X-Ray Repair Cross Complementing 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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BRCA1 mutation • BRCA2 mutation • HER-2 negative • PALB2 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • BARD1 mutation • MRE11A mutation • RAD50 mutation • BRCA mutation • FANCM mutation • RAD51 mutation
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Ibrance (palbociclib)
3ms
Characteristics of TNBC patients carrying other than BRCA gene mutations (SABCS 2021)
In conclusion, our results support the MGP using, opening the question about the 60-year cut off for genetic testing in TNBC, regardless of family history. Table 1: Characteristics of TNBC tumors in patients carrying other than BRCA gene mutations
Clinical • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • PMS2 (PMS1 protein homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • EPCAM (Epithelial cell adhesion molecule) • MUTYH (MutY homolog) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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TP53 mutation • BRCA1 mutation • BRCA2 mutation • HER-2 amplification • HER-2 overexpression • ATM mutation • PTEN mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • BARD1 mutation • BRCA mutation • ER expression • NBN mutation • RAD51 mutation
3ms
Pathognomonic long molecule footprints of backup repair pathways in homologous recombination deficient cancers (SABCS 2021)
These results provide direct genomic evidence linking large-scale structural changes in HR-deficient tumors with specific backup repair pathways that suggest novel, therapeutically targetable dependencies . Our findings elucidate backup repair mechanisms responsible for generating structural variation in HR-deficient tumors, demonstrate the genotype-specific divergence of such compensatory DNA repair, and provide genomic features that improve the detection accuracy of HR-deficiency with utility for the optimal selection of treatment.
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C)
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BRCA1 mutation • BRCA2 mutation • HRD • PALB2 mutation • RAD51C mutation • HRD + BRCA1 mutation
3ms
Precision Oncology of High-Grade Ovarian Cancer Defined through Targeted Sequencing. (PubMed, Cancers (Basel))
Tumours from 274 women were sequenced, including high-grade serous carcinoma (n = 252), clear cell carcinoma (n = 4), carcinosarcoma (n = 9), endometrioid carcinoma (n = 3), undifferentiated carcinoma (n = 1), and mixed tumours (n = 5). Genomic profiling did not influence histologic diagnosis. Mutations were identified in TP53, BRCA1, BRCA2, as well as additional homologous recombination repair pathway genes BARD1, ATR, CHEK2, PALB2, RAD51D, RAD50, SLX4, FANCA, RAD51C, and RAD54L. In addition, mutations in PTEN and CDKN2A were identified. Several somatic mutations with implications for germline testing were identified, including RMI1, STK11, and CDH1. Germline testing identified 16 previously unknown BRCA1/2 carriers. Finally, 20 patients were treated with the PARP inhibitor olaparib based on the sequencing results.
Journal • BRCA Biomarker • PARP Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1)
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TP53 mutation • BRCA1 mutation • PTEN mutation • PALB2 mutation • CDKN2A mutation • RAD51D mutation • RAD51C mutation • FANCA mutation • BARD1 mutation • RAD50 mutation • RAD51 mutation
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Lynparza (olaparib)
4ms
Germline RAD51B variants confer susceptibility to breast and ovarian cancers deficient in homologous recombination. (PubMed, NPJ Breast Cancer)
Furthermore, we demonstrate that tumors harboring biallelic RAD51B alteration are deficient in homologous recombination DNA repair deficiency (HRD), as evidenced by analysis of sequencing data and in vitro functional assays. Our findings suggest that RAD51B should be considered as an addition to clinical germline testing panels for breast and ovarian cancer susceptibility.
Journal
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RAD51B (RAD51 Paralog B) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
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DDR • RAD51D mutation • RAD51C mutation • RAD51 mutation
4ms
Clinical Impact of Pathogenic Germline Variants in Pancreatic Cancer: Results From a Multicenter, Prospective, Universal Genetic Testing Study. (PubMed, Clin Transl Gastroenterol)
Universal multigene panel testing in PC reveals that 1 in 6 patients are carriers of PGV. Multigene germline testing should be used to aid in treatment selection, prognostication, and familial cancer counseling.
Clinical • Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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BRCA1 mutation • PALB2 mutation • CHEK2 mutation • RAD51C mutation • NBN mutation
4ms
A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma (clinicaltrials.gov)
P2, N=43, Recruiting, Shadia Jalal, MD | Trial completion date: May 2022 --> May 2023 | Trial primary completion date: May 2021 --> May 2022
Clinical • Trial completion date • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • NBN mutation
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Zejula (niraparib)
4ms
Ovarian cancer specific BRCA-like copy number aberration classifiers detect mutations associated with homologous recombination deficiency in the AGO-TR1 trial. (PubMed, Clin Cancer Res)
The newly trained classifiers detected most BRCA-mutated and methylated cancers and all tumors harboring a RAD51C germline mutations. Beyond that, we found an additional substantial proportion of ovarian cancers to be BRCA-like.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset)
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BRCA1 mutation • BRCA2 mutation • HRD • RAD51C mutation • HRD + BRCA1 mutation • BRCA mutation • RAD51 mutation
4ms
A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)
P2, N=32, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2022 --> Feb 2023 | Trial primary completion date: Feb 2022 --> Feb 2023
Trial completion date • Trial primary completion date
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PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • BARD1 mutation • FANCA deletion
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Lynparza (olaparib) • Imfinzi (durvalumab)
5ms
Enrollment open
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression
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FoundationOne® CDx
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Trodelvy (sacituzumab govitecan-hziy) • berzosertib (M6620)
5ms
Clinical • New P2 trial
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HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCC (FA Complementation Group C)
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BRCA1 mutation • BRCA2 mutation • HER-2 amplification • HER-2 negative • ATM mutation • HRD • PALB2 mutation • ER positive + PGR positive • PGR positive • RAD51D mutation • CHEK2 mutation • RAD51C mutation • BARD1 mutation • RAD51 mutation
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Keytruda (pembrolizumab) • Lynparza (olaparib)
5ms
Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer With HRR Mutation and MSS (clinicaltrials.gov)
P1/2, N=71, Not yet recruiting, Yonsei University | Trial completion date: Dec 2022 --> May 2023 | Initiation date: May 2021 --> Oct 2021 | Trial primary completion date: Jul 2022 --> Dec 2022
Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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HER-2 positive • BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
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Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel
5ms
[VIRTUAL] HOMOLOGOUS RECOMBINATION REPAIR GENES TESTING IN A COHORT OF APULIAN OVARIAN CANCERS PATIENTS IN THE ROUTINE DIAGNOSTIC PROCEDURE (IGCS 2021)
We demonstrated that the usage of a multigene panel, beyond BRCA1/2, improves the diagnostic yield in OC testing and it could produce clinically relevant results.
Clinical • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
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BRCA1 mutation • BRCA2 mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • BARD1 mutation • RAD51 mutation
5ms
SUKSES-B2: Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects (clinicaltrials.gov)
P2, N=28, Recruiting, Se-Hoon Lee | Not yet recruiting --> Recruiting
Clinical • Enrollment open • Combination therapy
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • SLFN11 (Schlafen Family Member 11) • RAD51B (RAD51 Paralog B) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD54L (DNA Repair And Recombination Protein RAD54) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • WRN (WRN RecQ Like Helicase) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
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BRCA1 mutation • BRCA2 mutation • RAD51D mutation • RAD51C mutation • RAD51B mutation • MRE11A mutation • RAD50 mutation • RAD54L mutation • BLM mutation • BRCA mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
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Lynparza (olaparib) • Avastin (bevacizumab)
6ms
Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions. (PubMed, Int J Mol Sci)
Furthermore, there is not a statistically significant difference in the proportion of cases with a tumor onset under age of 40 between the two groups, but the presence of multiple non-coding variants in the same patient may affect the aggressiveness of the tumor and it is worth underlining that 25% of patients with an aggressive tumor are carriers of a PTEN 3'UTR-variant. This data provides initial information on how important it might be to extend mutational screening to the regulatory regions in clinical practice.
Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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BRCA1 mutation • BRCA2 mutation • PTEN mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD50 mutation • NBN mutation
6ms
Niraparib in Tumors Metastatic to the CNS (clinicaltrials.gov)
P2, N=20, Not yet recruiting, Massachusetts General Hospital
New P2 trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • XRCC2 (X-Ray Repair Cross Complementing 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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BRCA1 mutation • ATM mutation • HRD • PALB2 mutation • BAP1 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • HRD + BRCA1 mutation • MRE11A mutation • RAD50 mutation • RAD54L mutation • NBN mutation
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Zejula (niraparib)
6ms
Acquired RAD51C promoter methylation loss causes PARP inhibitor resistance in high grade serous ovarian carcinoma. (PubMed, Cancer Res)
PDX models lost meRAD51C following treatment with PARPi rucaparib or niraparib, where a single unmethylated copy of RAD51C was sufficient to drive PARPi resistance. Differences in methylation stability under treatment pressure were also observed between patients, where one HGSC was found to maintain meRAD51C after 6 lines of therapy (4 platinum-based), whilst another HGSC sample was found to have heterozygous meRAD51C and elevated RAD51C gene expression (relative to homozygous meRAD51C controls) after only neo-adjuvant chemotherapy. As meRAD51C loss in a single gene copy was sufficient to cause PARPi resistance in PDX, methylation zygosity should be carefully assessed in previously treated patients when considering PARPi therapy.
Journal • PARP Biomarker
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HRD (Homologous Recombination Deficiency) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
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HRD • RAD51C mutation • RAD51 mutation
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Zejula (niraparib) • Rubraca (rucaparib)
6ms
DIDO: Niraparib and Dostarlimab in HRD Solid Tumors (clinicaltrials.gov)
P2, N=30, Not yet recruiting, West Cancer Center
New P2 trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCI (FA Complementation Group I)
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BRCA1 mutation • ATM mutation • HRD • PALB2 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • HRD + BRCA1 mutation • RAD54L mutation • FANCI mutation • RAD51 mutation
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Zejula (niraparib) • Jemperli (dostarlimab)
6ms
Characterization of a RAD51C-silenced high-grade serous ovarian cancer model during development of PARP inhibitor resistance. (PubMed, NAR Cancer)
PH039 acquired PARPi resistance by the third treatment cycle and grew through subsequent treatment with either niraparib or rucaparib. Interestingly, the PARPi resistant PH039 model remained platinum sensitive. Collectively, these results not only indicate that PARPi treatment pressure can reverse RAD51C methylation and restore RAD51C expression, but also provide a model for studying the clinical observation that PARPi and platinum sensitivity are sometimes dissociated.
Preclinical • Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C)
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BRCA1 mutation • BRCA2 mutation • RAD51C mutation • RAD51 mutation • RAD51C expression
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Zejula (niraparib) • Rubraca (rucaparib)
6ms
[VIRTUAL] Germline mutations in homologous recombination repair (HRR) pathway in a Chinese multi-cancer retrospective analysis (ESMO 2021)
Recently, FDA has approved olaparib for adult patients (pts) with deleterious germline or somatic HRR gene-mutated metastatic castration-resistant prostate cancer... This study revealed the landscape of germline mutations in HRR pathway in Chinese cancer pts, which might result in more effective personalized diagnoses and therapies.
Retrospective data • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
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BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • BARD1 mutation
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Lynparza (olaparib)
6ms
[VIRTUAL] Analysis of germ-line mutations in non-syndromic malignancies with concurrent pathogenic variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, and RAD51C/D (ESMO 2021)
This small study demonstrates the relative frequency of germline BRCA1/2, PALB2, ATM, and CHEK2 in non-syndromic tumor types. The correlation between germline and somatic variants was most frequently noted for BRCA1, PALB2, and CHEK2.
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
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BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD51C mutation
6ms
[VIRTUAL] Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC): Exploratory biomarker analyses of the phase IIIb OPINION study (ESMO 2021)
Despite limitations in subgroup size, clinical benefit with maintenance olaparib was observed in non-gBRCAm pts with PSR OC, irrespective of biomarker status. Pts with a non-BRCA HRRm achieved longer PFS benefit compared with the non HRRm subgroup. TP53 mutation status was not predictive of olaparib sensitivity in this setting., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
P3 data • Clinical • PARP Biomarker • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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TP53 mutation • BRCA1 mutation • BRCA2 mutation • HRD • BRIP1 mutation • RAD51C mutation • BRCA1 mutation + BRCA2 mutation • HRD + BRCA1 mutation
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Myriad myChoice® CDx
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Lynparza (olaparib)
6ms
[VIRTUAL] Phase Ib study of venadaparib, a potent and selective PARP inhibitor, in homologous recombination repair (HRR) mutated breast cancer (ESMO 2021)
Venadaparib showed efficacy in gBRCAmt or sBRCAmt mBC patients. Preliminary efficacy findings suggest strong potency of venadaparib in g/sBRCAmt mBC, while preliminary safety findings are comparable to commercially available PARP inhibitors. These findings warrant further investigation of venadaparib in breast cancer beyond gBRCAmt.
P1 data • BRCA Biomarker • PARP Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset)
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BRCA1 mutation • BRCA2 mutation • HER-2 negative • ATM mutation • PALB2 mutation • RAD51C mutation • BRCA mutation • RAD51 mutation
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venadaparib (NOV 1401)
6ms
Clinical • New P2 trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • ATM positive
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docetaxel • senaparib (IMP4297)
7ms
[VIRTUAL] Identification of high-risk families with gynecological cancers and hereditary tumor syndrome (GSS 2021)
Summary Using the selection criterion, a pathogenic mutation could be detected in the TruRisk® panel analysis in 28.8% of the family members included. A mutation detection probability of at least 10% results from fulfilling the inclusion criteria of the GC-HBOC.
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD51C mutation • RAD51 mutation
7ms
A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency (clinicaltrials.gov)
P2, N=50, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Jun 2021 --> Sep 2020
Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
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BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • MYC amplification • CCNE1 amplification • FBXW7 mutation • RAD51D mutation • RAD51C mutation • RAD51 mutation
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prexasertib (LY2606368)
7ms
Clinical • New P2 trial • Combination therapy
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • SLFN11 (Schlafen Family Member 11) • RAD51B (RAD51 Paralog B) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD54L (DNA Repair And Recombination Protein RAD54) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • WRN (WRN RecQ Like Helicase) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
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BRCA1 mutation • BRCA2 mutation • RAD51D mutation • RAD51C mutation • RAD51B mutation • MRE11A mutation • RAD50 mutation • RAD54L mutation • BLM mutation • BRCA mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
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Lynparza (olaparib) • Avastin (bevacizumab)
8ms
Homologous recombination repair gene mutations in Chinese localized and locally advanced prostate cancer patients. (PubMed, Pathol Res Pract)
This study illustrated the mutation patterns of HRR genes in Chinese population with localized and locally advanced prostate cancer. These results provide further evidence that HRR gene mutations were more prevalent in patients with higher Gleason grade, or with very-high-risk level. Patients with these clinicopathologic characteristics may need more precise stratification through molecular detection.
Clinical • Journal • BRCA Biomarker • PARP Biomarker
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BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51C (RAD51 paralog C) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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PALB2 mutation • CDK12 mutation • RAD51C mutation • NBN mutation • RAD51 mutation
8ms
Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2022 --> Aug 2022 | Trial primary completion date: Aug 2021 --> Jan 2022
Trial completion date • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
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Lynparza (olaparib)
8ms
[VIRTUAL] Increased Activity of poly-ADP ribose polymerase (PARP) in peripheral blood lymphocytes predicts prostate cancer risk (EACR 2021)
Conclusion These findings demonstrates the potential of detecting PARP activities in PBLs as method to estimate prostate cancer susceptibility. Furthermore measurement of carboplatin-sensitivities and DSB-repair-activities might have the potential to further classify patients individually risk.
BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C)
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BRCA1 mutation • RAD51C mutation
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carboplatin
8ms
[VIRTUAL] Increased Activity of poly-ADP ribose polymerase (PARP) in peripheral blood lymphocytes predicts prostate cancer risk (EACR 2021)
Conclusion These findings demonstrates the potential of detecting PARP activities in PBLs as method to estimate prostate cancer susceptibility. Furthermore measurement of carboplatin-sensitivities and DSB-repair-activities might have the potential to further classify patients individually risk.
BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C)
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BRCA1 mutation • RAD51C mutation
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carboplatin
8ms
[VIRTUAL] Increased Activity of poly-ADP ribose polymerase (PARP) in peripheral blood lymphocytes predicts prostate cancer risk (EACR 2021)
Conclusion These findings demonstrates the potential of detecting PARP activities in PBLs as method to estimate prostate cancer susceptibility. Furthermore measurement of carboplatin-sensitivities and DSB-repair-activities might have the potential to further classify patients individually risk.
BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C)
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BRCA1 mutation • RAD51C mutation
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carboplatin
8ms
[VIRTUAL] Increased Activity of poly-ADP ribose polymerase (PARP) in peripheral blood lymphocytes predicts prostate cancer risk (EACR 2021)
Conclusion These findings demonstrates the potential of detecting PARP activities in PBLs as method to estimate prostate cancer susceptibility. Furthermore measurement of carboplatin-sensitivities and DSB-repair-activities might have the potential to further classify patients individually risk.
BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C)
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BRCA1 mutation • RAD51C mutation
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carboplatin
9ms
[VIRTUAL] Frequency of DNA repair gene mutations and impact on prognosis in HNSCC. (ASCO 2021)
A significant proportion of patients with HNSCC were found to have mutations in DRG . Patients with laryngeal disease were most likely to have DRG mutations, whereas those with oropharyngeal disease were less likely . Patients with DRG mutations in ctDNA, but not tDNA, had significantly worse prognoses with a lower likelihood of overall survival and higher disease burden at last visit.
PARP Biomarker • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • KMT2C (Lysine Methyltransferase 2C) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRCA1 mutation • ATM mutation • ARID1A mutation • PALB2 mutation • RAD51D mutation • RAD51C mutation • RAD51 mutation • CHEK1 expression • MLL3 mutation
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Guardant360® CDx
9ms
[VIRTUAL] Laboratory cross-comparison of homologous recombination repair mutation analysis in tumor in a multicenter epithelial ovarian cancer series: The BORNEO GEICO 60-0 study. (ASCO 2021)
In our EOC series the concordance of two Laboratories in the identification of clinically relevant HRR mutations on tumor is high but discrepancies in interpretation remain a challenge that needs further harmonization.
Clinical • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
9ms
[VIRTUAL] Frequency of homologous recombination repair alterations in ovarian cancer in Chinese population. (ASCO 2021)
CtDNA can characterize the mutational feature of HRR in OC . Around 42.3% of patients with OC harbour germline or somatic HRR mutations . The expanded use of PARP inhibitors in HRR deficient tumours using a signature of HRR by ctDNA in clinical practice requires validation.
Clinical • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54)
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BRCA1 mutation • ATM mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51B mutation • RAD54L mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
9ms
[VIRTUAL] Frequency of homologous recombination deficiency gene mutations in melanoma and its relevance to the immunotherapeutic response. (ASCO 2021)
Our data suggest that detection of somatic mutations in HRR genes might contribute to identify patients who might benefit from immune checkpoint blockade therapy . In addition, the molecular features of HRD provide new opportunities to predict the tumor response to multiple treatments.
BRCA Biomarker • IO biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRCA1 mutation • ATM mutation • HRD • PALB2 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • RAD51B mutation • HRD + BRCA1 mutation • CHEK1 expression
9ms
[VIRTUAL] Analysis of circulating tumor DNA identifies homologous recombination repair molecular features of Chinese breast cancer. (ASCO 2021)
CtDNA can characterize the mutational feature of HRR in BC . our study contributes to the understanding of the HRR pathways and specific genetic alterations harbored by Chinese patients with BC that could potentially be developed as markers of treatment response to targeted therapeutics . Ref: Razavi P, Chang MT, Xu GT, et al .
BRCA Biomarker • PARP Biomarker • Circulating tumor DNA
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
9ms
[VIRTUAL] Concurrent BRAFV600E and BRCA mutations in microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Prevalence and case series of mCRC (pts) with prolonged overall survival (OS). (ASCO 2021)
Co-existence of BRAF V600E/BRCA1/2 may represent a unique subset of advanced MSS CRC that may have a better prognosis and represent an opportunity to test novel targeted therapies . Larger prospective clinical validation trials in this subset is warranted.
Clinical • MSi-H Biomarker • BRCA Biomarker
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BRAF (B-raf proto-oncogene) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRAF V600E • BRCA1 mutation • BRCA2 mutation • MSI-H/dMMR • BRAF V600 • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • BRCA mutation • CHEK1 expression
9ms
[VIRTUAL] Clinical impact of pathogenic germline variants in pancreatic cancer: Results from a multicenter prospective universal genetic testing study. (ASCO 2021)
Universal multi-gene panel testing in pancreatic cancer reveals that 1 in 6 patients are carriers of PGV and is associated with improved survival . Multi-gene germline testing should be used to aid in treatment selection, prognostication, and familial cancer counseling . Distribution of the 40 PGV by penetrance status.
Clinical • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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PALB2 mutation • CHEK2 mutation • RAD51C mutation • NBN mutation
9ms
[VIRTUAL] Pathological complete response rate and survival in patients with BRCA-associated triple-negative breast cancer after 12 weeks of de-escalated neoadjuvant chemotherapy: Translational results of the WSG-ADAPT TN randomized phase II trial (NCT01815242). (ASCO 2021)
Background: The phase II trial WSG-ADAPT TN randomized triple-negative breast cancer (TNBC) patients to receive 12 weeks of neoadjuvant nab-paclitaxel (nab-pac) combined with carboplatin (carbo) vs gemcitabine (gem) and showed a substantial improvement of pathological complete response (pCR: ypT0/is, ypN0) with carbo (45.9% vs 28.7%) . Twelve weeks of neoadjuvant nab-pac/carbo is a highly effective anthracycline-free regimen that leads to an excellent pCR-rate of 64% in tumor BRCA1/2-mutated cases . BRCA1/2 mutation status could support this de-escalation strategy in early TNBC, but further prospective validation of survival impacts in larger cohorts and with longer follow up is needed . More detailed survival analyses will be presented at the meeting.
Clinical • P2 data • BRCA Biomarker
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • FANCM (FA Complementation Group M) • XRCC2 (X-Ray Repair Cross Complementing 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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TP53 mutation • ATM mutation • PTEN mutation • PTEN deletion • STK11 mutation • PALB2 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • BARD1 mutation • MRE11A mutation • RAD50 mutation • BRCA mutation • FANCM mutation • NBN mutation • RAD51 mutation
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carboplatin • gemcitabine • Abraxane (albumin-bound paclitaxel)
9ms
TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)
P2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Nov 2021 --> Nov 2022 | Trial primary completion date: May 2021 --> May 2022
Clinical • Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • RAD50 (RAD50 Double Strand Break Repair Protein) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCG (FA Complementation Group G) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
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RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • FANCF mutation • RAD50 mutation • FANCG mutation • FANCI mutation • FANCM mutation • NBN mutation
|
Rubraca (rucaparib)
9ms
Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer With HRR Mutation and MSS (clinicaltrials.gov)
P1/2, N=71, Recruiting, Yonsei University | Not yet recruiting --> Recruiting | Initiation date: Dec 2020 --> May 2021
Clinical • Enrollment open • Trial initiation date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
|
HER-2 positive • BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
|
Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel
9ms
[VIRTUAL] Deep Profiling of Immune Landscape as well as Immune Microenvironment of Asian Hereditary Ovarian and Breast Cancers (CSI-FCS 2020)
Further studies are on-going to interrogate the peripheral blood immune cells and other DNA damage relevant markers using techniques such as multi-coloured flow cytometry and multiplex cytokine profiling. We envision a strategic integration of liquid and tissue biopsies, providing a revolutionary strategy to empower novel diagnostic, prognostic and therapeutic strategies of Asian Hereditary Ovarian and Breast cancers.
BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRCA2 mutation • RAD51D mutation • RAD51C mutation
10ms
A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Patients With a Solid Tumor (SEASTAR) (clinicaltrials.gov)
P1b/2, N=329, Active, not recruiting, Clovis Oncology, Inc. | Recruiting --> Active, not recruiting
Enrollment closed
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRCA2 mutation • PALB2 mutation • RAD51D mutation • RAD51C mutation • RAD51 mutation
|
Rubraca (rucaparib) • Trodelvy (sacituzumab govitecan-hziy) • lucitanib (E 3810)
10ms
Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation. (PubMed, Cold Spring Harb Mol Case Stud)
Conversely, its position within a critical site suggests that it is refractory to secondary mutations that would restore RAD51C gene function and lead to therapy resistance. A need for a greater understanding of the relationship between mutation position and reversion potential of HR genes is underscored, as it may help predict the effectiveness of therapies in patients with HR-deficient cancers.
Clinical • Journal
|
RAD51B (RAD51 Paralog B) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • XRCC2 (X-Ray Repair Cross Complementing 2)
|
RAD51D mutation • RAD51C mutation • RAD51B mutation • RAD51 mutation
10ms
New trial
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
PALB2 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation
10ms
New P1/2 trial
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression
|
FoundationOne® CDx
|
Trodelvy (sacituzumab govitecan-hziy) • berzosertib (M6620)
11ms
ORCHID: Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (clinicaltrials.gov)
P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2022 --> Mar 2023 | Trial primary completion date: Mar 2021 --> Mar 2022
Clinical • Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
|
Lynparza (olaparib)
11ms
[VIRTUAL] Using whole-genome mutational signatures to predict homologous recombination repair deficiency in high grade serous ovarian carcinoma. (AACR 2021)
Our data indicate that HRD signatures are widespread in advanced HGSC. HRDetect-low may define a critical subset of patients with poor prognosis that are unlikely to benefit from PARP inhibitors and should be the focus of clinical trials for more appropriate adjunctive therapies. Additional studies are required to confirm the incidence of HRDetect and to correlate it with clinical response to PARP inhibitors in ovarian carcinoma.
BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
|
BRCA1 mutation • PTEN mutation • PALB2 mutation • RAD51D mutation • RAD51C mutation • BRCA1 hypermethylation • NBN mutation • RAD51 mutation
11ms
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2, N=30, Active, not recruiting, Massachusetts General Hospital | N=223 --> 30
Enrollment change
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • ARID1A mutation • MYC amplification • CDK12 mutation • CCNE1 amplification • ATRX mutation • BRIP1 mutation • FBXW7 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • FANCM mutation • NBN mutation
|
berzosertib (M6620)
11ms
Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Mar 2021 --> Aug 2021
Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
|
Lynparza (olaparib)
11ms
Recurrent Mutations in BRCA1, BRCA2, RAD51C, PALB2 and CHEK2 in Polish Patients with Ovarian Cancer. (PubMed, Cancers (Basel))
We found that pathogenic mutations in BRCA1, BRCA2, RAD51C or PALB2 are responsible for 12.5% of unselected cases of ovarian cancer. We recommend that all women with ovarian cancer in Poland and first-degree female relatives should be tested for this panel of 18 mutations.
Clinical • Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • BRCA2 mutation • PALB2 mutation • CHEK2 mutation • RAD51C mutation • RAD51 mutation
11ms
Germline mutations in RAD51C and RAD51D and hereditary predisposition to ovarian cancer. (PubMed, Klin Onkol)
Currently, identification of germline mutation in RAD51C and RAD51D is primarily of preventive importance but it potentially could make a prognostic difference. The aim of this review is to summarize the recent RAD51C and RAD51D knowledge, including the biological function, cancer risks associated with germline mutations, and recommendations for mutation carriers.
Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
RAD51D mutation • RAD51C mutation • RAD51 mutation
11ms
Clinical • New P2 trial • Pan tumor
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • CDK12 (Cyclin dependent kinase 12) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • ARID2 (AT-Rich Interaction Domain 2) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
|
HER-2 positive • HER-2 amplification • DDR • CDK12 mutation • PBRM1 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • BARD1 mutation • NBN mutation
|
Zejula (niraparib) • Jemperli (dostarlimab)
11ms
Mutations in DNA Repair Genes and Clinical Outcomes of Patients With Metastatic Colorectal Cancer Receiving Oxaliplatin or Irinotecan-containing Regimens. (PubMed, Am J Clin Oncol)
Mutations in DDR genes were present in 22% of patients with mCRC. In patients with DDR-mutated tumors, initial treatment with FOLFOX/XELOX correlated with improved OS and a numerically higher RR compared with FOLFIRI.
Clinical • Clinical data • Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
|
oxaliplatin • irinotecan
11ms
SUKSES-B: Olaparib Monotherapy in Relapsed Small Cell Lung Cancer Patients With HR Pathway Gene Mutations Not Limited to BRCA 1/2 Mutations, ATM Deficiency or MRE11A Mutations (clinicaltrials.gov)
P2, N=15, Completed, Samsung Medical Center | Recruiting --> Completed | N=28 --> 15 | Trial completion date: Sep 2021 --> Jan 2021 | Trial primary completion date: Sep 2021 --> Jan 2021
Clinical • Trial completion • Enrollment change • Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • RAD51B (RAD51 Paralog B) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD54L (DNA Repair And Recombination Protein RAD54) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • WRN (WRN RecQ Like Helicase) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
|
BRCA1 mutation • BRCA2 mutation • RAD51D mutation • RAD51C mutation • RAD51B mutation • MRE11A mutation • RAD50 mutation • RAD54L mutation • BLM mutation • WRN mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation • RPA1 mutation
|
Lynparza (olaparib)
12ms
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2, N=223, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting
Enrollment closed
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • ARID1A mutation • MYC amplification • CDK12 mutation • CCNE1 amplification • ATRX mutation • BRIP1 mutation • FBXW7 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • FANCM mutation • NBN mutation
|
berzosertib (M6620)
12ms
[VIRTUAL] Generation and characterisation of a unique cohort of rare gynaecological cancer patient-derived xenograft models (LCC 2021)
Molecular aberrations harboured by these PDX include mutations in BRCA1/2, BRIP1, AKT, PIK3CA; amplifications in CCNE1, MYC, EGFR; methylation of BRCA1 or RAD51C; mutational signature 3 (HRD); BRCA1 D11q expression and BRCA2 secondary mutations. A summary of the PDX cohort characterisation, including relevant drug response and relevance for patient outcome will be presented.
BRCA Biomarker
|
EGFR (Epidermal growth factor receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CCNE1 (Cyclin E1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • BRCA2 mutation • EGFR mutation • PIK3CA mutation • CCNE1 amplification • PIK3CA amplification • BRIP1 mutation • RAD51C mutation • BRCA1 expression • BRCA2 expression • RAD51 mutation
12ms
[VIRTUAL] Racial Disparities in Prevalence of Homologous Recombination Deficiency in Ovarian, Uterine, and Cervical Cancer Tumors (SGO 2021)
The observed racial differences in the distribution of somatic mutations in HRD across gynecologic malignancies merits further investigation to tailor treatment selection to target these Defects.
BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset)
|
BRCA1 mutation • BRCA2 mutation • PTEN mutation • HRD • CDK12 mutation • PTEN expression • RAD51C mutation • HRD + BRCA1 mutation • BRCA mutation • BRCA2 expression
1year
BRIP1, RAD51C, and RAD51D mutations are associated with high susceptibility to ovarian cancer: mutation prevalence and precise risk estimates based on a pooled analysis of ~30,000 cases. (PubMed, J Ovarian Res)
The meta-analysis provides evidence supporting the pathogenicity of BRIP1, RAD51C, and RAD51D mutations in relation to ovarian cancer. The level of ovarian cancer risk conferred by these mutations is relatively high, indicating that after BRCA1 and BRCA2, the BRIP1, RAD51C, and RAD51D genes are the most important ovarian cancer risk genes, cumulatively contributing to ~ 2% of ovarian cancer cases. The inclusion of the genes into routine diagnostic tests may influence both the prevention and the potential treatment of ovarian cancer.
Retrospective data • Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • RAD51 mutation
1year
[VIRTUAL] Clinical management and genomic profiling of paediatric low-grade gliomas in Saudi Arabia (ECP 2020)
Taken together, we reveal the genetic characteristics of pLGG patients can enhance diagnostics and therapeutic decisions. In addition, we identified a GOPC-ROS1 fusion that may be a biomarker for pLGG.
Clinical
|
BRAF (B-raf proto-oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NOTCH1 (Notch 1) • KIAA1549 • RNF43 (Ring Finger Protein 43) • RAD51C (RAD51 paralog C)
|
NTRK2 fusion • ATM mutation • ROS1 fusion • KIAA1549-BRAF fusion • BRAF fusion • RAD51C mutation • RNF43 mutation • GOPC-ROS1 fusion • RAD51 mutation
1year
[VIRTUAL] Clinical management and genomic profiling of paediatric low-grade gliomas in Saudi Arabia (ECP 2020)
Taken together, we reveal the genetic characteristics of pLGG patients can enhance diagnostics and therapeutic decisions. In addition, we identified a GOPC-ROS1 fusion that may be a biomarker for pLGG.
Clinical
|
BRAF (B-raf proto-oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NOTCH1 (Notch 1) • KIAA1549 • RNF43 (Ring Finger Protein 43) • RAD51C (RAD51 paralog C)
|
NTRK2 fusion • ATM mutation • ROS1 fusion • KIAA1549-BRAF fusion • BRAF fusion • RAD51C mutation • RNF43 mutation • GOPC-ROS1 fusion • RAD51 mutation
1year
[VIRTUAL] Clinical management and genomic profiling of paediatric low-grade gliomas in Saudi Arabia (ECP 2020)
Taken together, we reveal the genetic characteristics of pLGG patients can enhance diagnostics and therapeutic decisions. In addition, we identified a GOPC-ROS1 fusion that may be a biomarker for pLGG.
Clinical
|
BRAF (B-raf proto-oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NOTCH1 (Notch 1) • KIAA1549 • RNF43 (Ring Finger Protein 43) • RAD51C (RAD51 paralog C)
|
NTRK2 fusion • ATM mutation • ROS1 fusion • KIAA1549-BRAF fusion • BRAF fusion • RAD51C mutation • RNF43 mutation • GOPC-ROS1 fusion • RAD51 mutation
1year
RAD51-Mediated DNA Homologous Recombination Is Independent of PTEN Mutational Status. (PubMed, Cancers (Basel))
Our findings demonstrate definitively that PTEN loss does not alter the RAD51 expression, its paralogs, or the HR activity. Furthermore, deficiency in PTEN alone is not sufficient to impart enhanced sensitivity to PARPi associated with HRD. This study is the first to unequivocally demonstrate that PTEN deficiency is not linked to the RAD51 expression or the HR activity amongst primary neural and non-neural Pten-null cells, PTEN-deficient tumor cell lines, and primary PTEN-mutant GBM patient-derived tissue specimens and BTICs.
Journal • BRCA Biomarker • PARP Biomarker
|
PTEN (Phosphatase and tensin homolog) • RAD51B (RAD51 Paralog B) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset)
|
PTEN mutation • PTEN loss • PTEN expression • RAD51D mutation • RAD51C mutation • RAD51B mutation • BRCA mutation • RAD51 mutation
|
Lynparza (olaparib)
1year
Pathology of Hereditary Breast and Ovarian Cancer. (PubMed, Front Oncol)
Besides BRCA1 and BRCA2 mutations, alterations in a number of other homologous recombination genes with moderate penetrance, including PALB2, RAD51C, RAD51D, BRIP1, and others, have also been described in HBOC patients with varying frequency; however, distinct morphological characteristics of these tumors have not been well characterized to date. In this review, the above pathological features are discussed in detail and a focus is placed on how accurate pathologic interpretation plays an important role in allowing HBOC patients to receive the best possible management.
Journal • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset)
|
BRCA1 mutation • BRCA2 mutation • HER-2 expression • BRIP1 mutation • RAD51D mutation • RAD51C mutation • BRCA1 mutation + BRCA2 mutation • TILs
1year
[VIRTUAL] Histopathological results after risk-reducing bilateral salpingo-oophorectomy in BRCA1/2 mutation carriers: single center experience (ESGO 2020)
It is from tremendous importance to raise awareness that in women at high risk, the development of premalignant neoplasms and malignancies can be prevented. Timing of RRSO should be independent of age and promptly after completion of family planning
Clinical • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • BRCA2 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • BRCA1 mutation + BRCA2 mutation • RAD51 mutation
over1year
A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)
P2, N=32, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2021 --> Feb 2022 | Trial primary completion date: Feb 2021 --> Feb 2022
Trial completion date • Trial primary completion date • PARP Biomarker • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • BARD1 mutation • FANCA deletion
|
Lynparza (olaparib) • Imfinzi (durvalumab)
over1year
Clinical • New P1/2 trial • Combination therapy • PARP Biomarker • PD(L)-1 Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
|
HER-2 positive • BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
|
Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel
over1year
Effect of germline mutations in homologous recombination repair genes on overall survival of patients with pancreatic adenocarcinoma. (PubMed, Clin Cancer Res)
This study demonstrates that germline mutation carrier status in PDAC is associated with longer OS compared to non-carriers. Further research into tumor biology and response to platinum-based chemotherapy in germline mutation carriers with PDAC are needed to better understand the association with longer OS.
Clinical • Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • RAD51D mutation • RAD51C mutation • BARD1 mutation
over1year
[VIRTUAL] Exploratory biomarker analysis of Young-PEARL [palbociclib plus exemestane with GnRH agonist versus capecitabine in premenopausal women with HR (hormone receptor)-positive, HER2-negative metastatic breast cancer (MBC)] study (SABCS 2020)
The alteration of a few genes including Rb1 loss may be associated with resistance of palbociclib in HR-positive premenopausal population with MBC. Luminal type showed better prognosis, and BRCA2 pathogenic mutation showed worse prognosis regardless luminal/non-luminal type. ESR1 mutation was found in low population frequency because all patients didn’t received AI therapy.
Clinical • Tumor Mutational Burden • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • NOTCH2 (Notch 2) • RAD51C (RAD51 paralog C) • AURKA (Aurora kinase A) • BRCA (Breast cancer early onset) • GATA3 (GATA binding protein 3)
|
TP53 mutation • BRCA2 mutation • TMB-H • HR positive • HER-2 negative • PIK3CA mutation • ER mutation • RAD51C mutation • BRCA mutation • RAD51 mutation
|
Ibrance (palbociclib) • capecitabine
over1year
[VIRTUAL] Comparison of genomic instability test scores used for predicting PARP activity in ovarian cancer (IGCS 2020)
Among patients with positive HRD scores, up to 51% were negative by %LOH and up to 63% were negative by the 11-gene panel. Only 3% of patients identified as positive by %LOH and 7% positive by the 11-gene panel were negative by HRD score. Conclusions/Implications: These data show that HR deficiency tests used in clinical trials are not equivalent and should not be considered interchangeable in predicting PARP inhibitor response in clinical practice.
BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • MRE11A (MRE11 homolog, double strand break repair nuclease) • BARD1 (BRCA1 Associated RING Domain 1)
|
ATM mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • BARD1 mutation • MRE11A mutation • NBN mutation
over1year
[VIRTUAL] Low BRCA 1/2 germline mutation rate in a french canadian population. (IGCS 2020)
Based on Health Canada’s current approval, only a small proportion of our patients could access PARPi therapy. Hopefully canadian indications for PARPi will soon include non-BRCA and somatic mutations.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • MSH6 (MutS homolog 6) • CDH1 (Cadherin 1) • PMS2 (PMS1 protein homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MUTYH (MutY homolog)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • BRCA mutation • PMS2 mutation • RAD51 mutation
over1year
Management of high, moderate, and low penetrance ovarian cancer susceptibility mutations: an assessment of current risk reduction practices. (PubMed, Int J Gynecol Cancer)
Respondents were more likely to perform risk reducing salpingo-oophorectomy, in the setting of a BRCA1, RAD51C, and ATM mutation, earlier and more frequently in the setting of a BRCA1 mutation. However, there was a lack of consensus about management of the moderate and low penetrance mutations, suggesting that more data regarding age specific risks and appropriate risk reduction strategies for these alterations are needed.
Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • RAD51C mutation • RAD51 mutation
over1year
Association of RAD51C germline mutations with breast cancer among Bahamians. (PubMed, Breast Cancer Res Treat)
These data support increasing evidence that RAD51C mutations contribute to breast cancer susceptibility, although the impact may vary substantially from country to country.
Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C)
|
RAD51C mutation • RAD51 mutation
over1year
Clinical • New P2 trial • BRCA Biomarker • PARP Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • WRN (WRN RecQ Like Helicase) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
|
HER-2 positive • BRCA1 mutation • BRCA2 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • BARD1 mutation • FANCF mutation • HR positive + HER-2 negative • MRE11A mutation • RAD50 mutation • BLM mutation • CHEK1 mutation • FANCM mutation • NBN mutation • CHEK1 expression
|
Herceptin (trastuzumab) • Zejula (niraparib) • pucotenlimab (HX008)
over1year
Germline Genetic Findings Which May Impact Therapeutic Decisions in Families with a Presumed Predisposition for Hereditary Breast and Ovarian Cancer. (PubMed, Cancers (Basel))
Some of these molecular results could contribute to cancer diagnosis, treatment selection and prevention. We found a statistically significant association between tumour diversity in the family and carrying a variant with a high score predicting pathogenicity (p = 0.0003).
Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • BARD1 mutation • RAD51 mutation
over1year
[VIRTUAL] Clinical significance of structural variations in ATM, BRCA1, BRCA2 and RAD51C for Chinese patients with solid tumour (ESMO 2020)
Legal entity responsible for the study: Sun Yat-sen University Cancer Center. Funding: Has not received any funding.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset)
|
RAD51C mutation • RAD51 mutation
over1year
[VIRTUAL] Rucaparib + sacituzumab govitecan (SG): Initial data from the phase Ib/II SEASTAR study (NCT03992131) (ESMO 2020)
Tumour-targeted delivery of a TOP1 inhibitor may reduce systemic toxicity of the combination; thus, we evaluated the PARPi rucaparib + SG, an antibody-drug conjugate composed of an anti-Trop2 antibody coupled to the active metabolite of irinotecan (SN-38) via a unique hydrolyzable linker...Three pts had a confirmed PR, including 2 pts previously treated with niraparib until PD; 2 responders did not have HRR gene mutations...Funding: Clovis Oncology, Inc. Clinical trial identification: NCT03992131.
P1/2 data • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRCA2 mutation • PALB2 mutation • RAD51C mutation
|
Zejula (niraparib) • Rubraca (rucaparib) • irinotecan • Trodelvy (sacituzumab govitecan-hziy)
over1year
DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome. (PubMed, Cancers (Basel))
The most important genes of the DNA repair system are emphasized and their targeting in ovarian cancer will deserve further attention. The function of those genes, as well as the functional status of the entire DNA repair pathways, should be investigated in detail in the near future.
Review • Journal • BRCA Biomarker
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRCA2 mutation • BRAF mutation • PTEN mutation • RAD51C mutation • RAD51 mutation
over1year
Genomic Methods Identify Homologous Recombination Deficiency in Pancreas Adenocarcinoma and Optimize Treatment Selection. (PubMed, Clin Cancer Res)
Pathogenic HRm identifies HRD in patients with PDAC with the best outcome when treated with 1L-platinum. Biallelic HRm and core HRm further enriched benefit from 1L-platinum from HRD.
Journal • Tumor Mutational Burden • BRCA Biomarker
|
TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BAP1 (BRCA1 Associated Protein 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • HRD • PALB2 mutation • BAP1 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • BARD1 mutation • RAD50 mutation • BLM mutation • NBN mutation
over1year
[VIRTUAL] Application of an ovarian cancer histology-based testing strategy for BRCA1/2 variant detection (AACR-II 2020)
Olaparib was given to 20 patients, of which 17 had a demonstrated BRCA1,2 pathogenic mutation...Interestingly, patients who received PARPi therapy was slightly enriched for somatic variants (Total cohort 33/47; 70% germline, PARPi treated 9/17; 53% germline, not significant). Tumor testing allowed a number previously unidentified BRCA1/2 syndrome carriers to be identified.
BRCA Biomarker • PARP Biomarker
|
TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • CDH1 (Cadherin 1) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • ATR (Ataxia telangiectasia and Rad3-related protein) • FANCM (FA Complementation Group M)
|
TP53 mutation • BRCA1 mutation • RAD51D mutation • RAD51C mutation • FANCA mutation • BLM mutation • FANCM mutation • RAD51 mutation
|
Lynparza (olaparib)
over1year
[VIRTUAL] Exceptional sustained responses to ipilimumab/nivolumab (ipi/nivo) in patients (pts) with advanced pancreaticobiliary cancers and germline DNA damage repair (DDR) mutations. (ASCO 2020)
One pt with a CR had gBRCA1 with pancreatic adenocarcinoma (PDAC) s/p distal pancreatectomy/splenectomy, adjuvant gemcitabine (gem)/capecitabine, biopsy-proven recurrence in lung and retroperitoneum 12m later, initiated ipi/nivo, and achieved a CR ongoing for 22m on nivo maintenance. Second pt with a CR had gBRCA1 and unresectable cholangiocarcinoma (CC), with disease progression after gem/cisplatin (cis), therapy switched to ipi/nivo...The pt with a PR had RAD51C and metastatic PDAC s/p FOLFIRINOX for 6m, followed by olaparib for 12m. At progression, disease rapidly progressed through 5-fluorouracil/nanoliposomal irinotecan, gem/nab-paclitaxel/cis, and FOLFIRINOX... In this series, 6 out of 8 evaluable pts with advanced pancreaticobiliary cancers had disease control with ipi/nivo. This series suggests that tumors with germline DDR mutations may be responsive to ICIs. Further evaluation is warranted.
Clinical • Tumor Mutational Burden • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
RAD51D mutation • RAD51C mutation
|
Opdivo (nivolumab) • Lynparza (olaparib) • cisplatin • Yervoy (ipilimumab) • gemcitabine • capecitabine • Abraxane (albumin-bound paclitaxel) • Onivyde (nanoliposomal irinotecan) • fluorouracil topical
over1year
[VIRTUAL] Germline and somatic mutations in 25 hereditary breast and ovarian cancer related genes and platinum-based chemotherapy response among Chinese patients with epithelial ovarian cancer. (ASCO 2020)
Multi-gene panel testing of germline and somatic HBOC related gene mutations was feasible to characterize a comprehensive molecular profile of ovarian cancer and showed non-BRCA gene stratification potential value in predicting patient’s response for platinum-based chemotherapy. Research Funding: None
Clinical • BRCA Biomarker
|
TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • MRE11A (MRE11 homolog, double strand break repair nuclease) • BARD1 (BRCA1 Associated RING Domain 1)
|
TP53 mutation • BRCA1 mutation • ATM mutation • PTEN mutation • PALB2 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • BARD1 mutation • MRE11A mutation
over1year
[VIRTUAL] Prevalence of BRCA1 and BRCA 2 and other mutations in Chilean population. (ASCO 2020)
The highest percentage of patient care was for women with breast cancer, under 50 years of age. The overall test positivity rate is a cumulative 29%. Mutations in BRCA 1 and BRCA 2 were the most detected mutations, as reported in the literature.
Clinical • BRCA Biomarker
|
TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • MSH2 (MutS Homolog 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • MUTYH (MutY homolog)
|
TP53 mutation • BRCA1 mutation • BRCA2 mutation • ATM mutation • RAD51D mutation • RAD51C mutation • BRCA mutation
over1year
[VIRTUAL] The prognostic value of HRD mutations in liver cancer. (ASCO 2020)
HRD mutations are significantly associated with a shorter OS in liver cancer patients. HRD mutation was a negative prognostic factor for overall survival in liver cancer, but the underlying mechanisms remain to be explored. Research Funding: None
BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • BARD1 (BRCA1 Associated RING Domain 1)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • HRD • PALB2 mutation • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • BARD1 mutation • CHEK1 mutation • NBN mutation • CHEK1 expression
over1year
[VIRTUAL] Characters of germline mutations in Chinese non-small cell lung cancer patients. (ASCO 2020)
In this study, there is no significant correlation of germline susceptibility gene mutations with clinical and genetic characters of NSCLC patients. Further investigation on germline genetic aberrations of NSCLC is definitely needed to clarify germline impact on the etiology of NSCLC. Research Funding: None
Clinical • BRCA Biomarker
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • ATR (Ataxia telangiectasia and Rad3-related protein) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD50 (RAD50 Double Strand Break Repair Protein) • MUTYH (MutY homolog) • PMS1 (PMS1 protein homolog 1)
|
KRAS mutation • BRCA2 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • MRE11A mutation • RAD50 mutation • BLM mutation • PMS1 mutation
over1year
[VIRTUAL] Genetic testing and referral patterns of non-BRCA mutation carriers at increased or uncertain risk of ovarian cancer. (ASCO 2020)
Only ~30% of pts underwent GT by a GC, which was associated with increased referral to a GO. LS genes are better known and were associated with higher uptake of GO referral. Education of OC risks of these newer mutations among providers performing GT may increase referral to a GO and uptake of RRS.
BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • BARD1 (BRCA1 Associated RING Domain 1) • EPCAM (Epithelial cell adhesion molecule)
|
ATM mutation • STK11 mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • MSH2 mutation • RAD51C mutation • BARD1 mutation • PMS2 mutation • NBN mutation
over1year
[VIRTUAL] Comparison of genomic instability test scores used for predicting PARP activity in ovarian cancer. (ASCO 2020)
These data show that HRD tests used in published and ongoing clinical trials are not equivalent, and they should not be considered interchangeable in predicting PARP inhibitor response in clinical practice. *Could not be calculated because positive results by the 11-gene panel were not continuous Research Funding: Myriad Genetic Laboratories, Inc.
BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MRE11A (MRE11 homolog, double strand break repair nuclease) • BARD1 (BRCA1 Associated RING Domain 1) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • HRD • BRIP1 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • BARD1 mutation • MRE11A mutation • NBN mutation
almost2years
[VIRTUAL] Postprogression outcomes in patients with ovarian carcinoma associated with a mutation in a non-BRCA homologous recombination repair gene receiving rucaparib maintenance treatment: Results from the phase III study ARIEL3 (SGO-I 2020)
Although the number of patients in this subgroup was small, rucaparib improved the clinically meaningful endpoints CFI, TFST, PFS2, and TSST versus placebo in patients with platinum-sensitive, recurrent ovarian cancer harboring a non-BRCA HRR gene mutation. Mutations in a subset of HRR genes, such as RAD51C/D, may confer greater sensitivity to PARP inhibitor treatment.
Clinical • P3 data • BRCA Biomarker • PARP Biomarker
|
BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset)
|
BRIP1 mutation • RAD51D mutation • RAD51C mutation
|
Rubraca (rucaparib)
almost2years
Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia. (PubMed, PLoS One)
Taken together, we reveal the genetic characteristics of pLGG patients can enhance diagnostics and therapeutic decisions. In addition, we identified a GOPC-ROS1 fusion that may be a biomarker for pLGG.
Clinical • Retrospective data • Journal
|
BRAF (B-raf proto-oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NOTCH1 (Notch 1) • RNF43 (Ring Finger Protein 43) • RAD51C (RAD51 paralog C)
|
NTRK2 fusion • ATM mutation • ROS1 fusion • BRAF fusion • RAD51C mutation • RNF43 mutation
almost2years
Multigene Panel Germline Testing of 1333 Czech Patients with Ovarian Cancer. (PubMed, Cancers (Basel))
Analysis of remaining 201 genes revealed somatic mosaics in PPM1D and germline mutations in SHPRH and NAT1 associating with a high/moderate OC risk significantly; however, further studies are warranted to delineate their contribution to OC development in other populations. Our findings demonstrate the high proportion of patients with hereditary OC in Slavic population justifying genetic testing in all patients with OC, including BTO.
Clinical • Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
|
BRCA1 mutation • BRCA2 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • BARD1 mutation • NBN mutation • PPM1D mutation
almost2years
Analysis of BRCA1 and RAD51C Promoter Methylation in Italian Families at High-Risk of Breast and Ovarian Cancer. (PubMed, Cancers (Basel))
Based on these observations; the analysis of constitutional methylation at promoters of these genes does not seem to substantially improve the definition of cancer risks in patients. These data support the idea that epimutations represent a very rare event in high-risk BC/OC populations.
Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset)
|
RAD51C mutation
almost2years
Exploring the Role of Mutations in Fanconi Anemia Genes in Hereditary Cancer Patients. (PubMed, Cancers (Basel))
Two patients with early-onset cancer showed a pathogenic FA variant in addition to another germline mutation, suggesting a modifier role for FA variants. Our results encourage a comprehensive analysis of FA genes in larger studies to better assess their role in cancer risk.
Clinical • Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • BRCA2 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • FANCF mutation
almost2years
Germline pathogenic variants in BRCA1, BRCA2, PALB2 and RAD51C in breast cancer women from Argentina. (PubMed, Breast Cancer Res Treat)
A founder mutation in PALB2 accounts for up to 4% of breast cancer patients in Argentina. BRCA1, BRCA2, PALB2 and RAD51C should be included in the genetic testing panel of breast cancer patients in Argentina.
Clinical • Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C)
|
PALB2 mutation • RAD51C mutation
almost2years
Mutations in HRD-associated genes in ovarian cancer patients: Expanding PARP inhibitor eligibility (SGO 2020)
Among patients with ovarian cancer, somatic, or germline mutations in non-BRCA1 and BRCA2 HRD genes are rare, detected in less than 5% of tumors. Although PARPi may benefit this patient population, our data suggest they represent a small percentage of ovarian cancer patients. Further study confirming these data in a larger cohort of ovarian cancer patients as well as testing efficacy of PARPi in these patients is needed.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • HRD • BRIP1 mutation • RAD51C mutation
almost2years
The predictive value of homologous recombination deficiency (HRD) status for progression free survival (PFS) after first-line platinum-based chemotherapy in advanced ovarian cancer (SGO 2020)
All received platinum-based chemotherapy; 13 also received intraperitoneal cisplatin; and 3 did not have debulking surgery... Ovarian cancer with HRD+ status was more likely to have intermediate levels of TMB and germline mutations. Mucinous and clear cell cancer had HRD− status. However, HRD+ status was not associated with more favorable outcome after platinum treatment or OS.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • HRD • BRIP1 mutation • RAD51C mutation
|
cisplatin
almost2years
Assessment of genetic testing rates in ovarian cancer patients (SGO 2020)
In our cohort, only 71.6% of epithelial ovarian cancer patients underwent genetic testing. The most common reason for noncompletion was clinical team-related factors, which should be the focus of future quality improvement measures, including maintaining physician awareness and improving data-recording techniques.
Clinical • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • MLH1 (MutL homolog 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • CHEK2 mutation • RAD51C mutation • MLH1 mutation
almost2years
Characterization of homologous recombination deficiency in uncommon epithelial ovarian cancer subtypes (SGO 2020)
High HRD scores were most common in ovarian cancers with high-grade mixed histology. Additional studies with larger cohorts are needed to confirm differences in HR defects or related tumor characteristics in mixed histology compared to pure high-grade serous ovarian cancers. In addition, understanding the underlying aberrations that contributing to HR defects provides important information for treatment and prevention.
BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • BRCA2 mutation • HRD • RAD51C mutation • NBN mutation
almost2years
Mutations in HRD-associated genes in ovarian cancer patients: Expanding PARP inhibitor eligibility (SGO 2020)
Among patients with ovarian cancer, somatic, or germline mutations in non-BRCA1 and BRCA2 HRD genes are rare, detected in less than 5% of tumors. Although PARPi may benefit this patient population, our data suggest they represent a small percentage of ovarian cancer patients. Further study confirming these data in a larger cohort of ovarian cancer patients as well as testing efficacy of PARPi in these patients is needed.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • HRD • BRIP1 mutation • RAD51C mutation
almost2years
Characterization of homologous recombination deficiency in uncommon epithelial ovarian cancer subtypes (SGO 2020)
High HRD scores were most common in ovarian cancers with high-grade mixed histology. Additional studies with larger cohorts are needed to confirm differences in HR defects or related tumor characteristics in mixed histology compared to pure high-grade serous ovarian cancers. In addition, understanding the underlying aberrations that contributing to HR defects provides important information for treatment and prevention.
BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • BRCA2 mutation • HRD • RAD51C mutation • NBN mutation
almost2years
The predictive value of homologous recombination deficiency (HRD) status for progression free survival (PFS) after first-line platinum-based chemotherapy in advanced ovarian cancer (SGO 2020)
All received platinum-based chemotherapy; 13 also received intraperitoneal cisplatin; and 3 did not have debulking surgery... Ovarian cancer with HRD+ status was more likely to have intermediate levels of TMB and germline mutations. Mucinous and clear cell cancer had HRD− status. However, HRD+ status was not associated with more favorable outcome after platinum treatment or OS.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • HRD • BRIP1 mutation • RAD51C mutation
|
cisplatin
almost2years
Assessment of genetic testing rates in ovarian cancer patients (SGO 2020)
In our cohort, only 71.6% of epithelial ovarian cancer patients underwent genetic testing. The most common reason for noncompletion was clinical team-related factors, which should be the focus of future quality improvement measures, including maintaining physician awareness and improving data-recording techniques.
Clinical • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • MLH1 (MutL homolog 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • CHEK2 mutation • RAD51C mutation • MLH1 mutation
almost2years
The predictive value of homologous recombination deficiency (HRD) status for progression free survival (PFS) after first-line platinum-based chemotherapy in advanced ovarian cancer (SGO 2020)
All received platinum-based chemotherapy; 13 also received intraperitoneal cisplatin; and 3 did not have debulking surgery... Ovarian cancer with HRD+ status was more likely to have intermediate levels of TMB and germline mutations. Mucinous and clear cell cancer had HRD− status. However, HRD+ status was not associated with more favorable outcome after platinum treatment or OS.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • HRD • BRIP1 mutation • RAD51C mutation
|
cisplatin
almost2years
Mutations in HRD-associated genes in ovarian cancer patients: Expanding PARP inhibitor eligibility (SGO 2020)
Among patients with ovarian cancer, somatic, or germline mutations in non-BRCA1 and BRCA2 HRD genes are rare, detected in less than 5% of tumors. Although PARPi may benefit this patient population, our data suggest they represent a small percentage of ovarian cancer patients. Further study confirming these data in a larger cohort of ovarian cancer patients as well as testing efficacy of PARPi in these patients is needed.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • HRD • BRIP1 mutation • RAD51C mutation
almost2years
Assessment of genetic testing rates in ovarian cancer patients (SGO 2020)
In our cohort, only 71.6% of epithelial ovarian cancer patients underwent genetic testing. The most common reason for noncompletion was clinical team-related factors, which should be the focus of future quality improvement measures, including maintaining physician awareness and improving data-recording techniques.
Clinical • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • MLH1 (MutL homolog 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • CHEK2 mutation • RAD51C mutation • MLH1 mutation
almost2years
Characterization of homologous recombination deficiency in uncommon epithelial ovarian cancer subtypes (SGO 2020)
High HRD scores were most common in ovarian cancers with high-grade mixed histology. Additional studies with larger cohorts are needed to confirm differences in HR defects or related tumor characteristics in mixed histology compared to pure high-grade serous ovarian cancers. In addition, understanding the underlying aberrations that contributing to HR defects provides important information for treatment and prevention.
BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • BRCA2 mutation • HRD • RAD51C mutation • NBN mutation
almost2years
Characterization of homologous recombination deficiency in uncommon epithelial ovarian cancer subtypes (SGO 2020)
High HRD scores were most common in ovarian cancers with high-grade mixed histology. Additional studies with larger cohorts are needed to confirm differences in HR defects or related tumor characteristics in mixed histology compared to pure high-grade serous ovarian cancers. In addition, understanding the underlying aberrations that contributing to HR defects provides important information for treatment and prevention.
BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • BRCA2 mutation • HRD • RAD51C mutation • NBN mutation
almost2years
The predictive value of homologous recombination deficiency (HRD) status for progression free survival (PFS) after first-line platinum-based chemotherapy in advanced ovarian cancer (SGO 2020)
All received platinum-based chemotherapy; 13 also received intraperitoneal cisplatin; and 3 did not have debulking surgery... Ovarian cancer with HRD+ status was more likely to have intermediate levels of TMB and germline mutations. Mucinous and clear cell cancer had HRD− status. However, HRD+ status was not associated with more favorable outcome after platinum treatment or OS.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • HRD • BRIP1 mutation • RAD51C mutation
|
cisplatin
almost2years
Mutations in HRD-associated genes in ovarian cancer patients: Expanding PARP inhibitor eligibility (SGO 2020)
Among patients with ovarian cancer, somatic, or germline mutations in non-BRCA1 and BRCA2 HRD genes are rare, detected in less than 5% of tumors. Although PARPi may benefit this patient population, our data suggest they represent a small percentage of ovarian cancer patients. Further study confirming these data in a larger cohort of ovarian cancer patients as well as testing efficacy of PARPi in these patients is needed.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • HRD • BRIP1 mutation • RAD51C mutation
almost2years
Assessment of genetic testing rates in ovarian cancer patients (SGO 2020)
In our cohort, only 71.6% of epithelial ovarian cancer patients underwent genetic testing. The most common reason for noncompletion was clinical team-related factors, which should be the focus of future quality improvement measures, including maintaining physician awareness and improving data-recording techniques.
Clinical • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • MLH1 (MutL homolog 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C)
|
BRCA1 mutation • CHEK2 mutation • RAD51C mutation • MLH1 mutation
almost2years
[VIRTUAL] Characterization of patients (pts) with long-term responses to rucaparib in recurrent ovarian cancer (OC). (ASCO 2020)
Long-term responders to rucaparib include OC with BRCA mutation, particularly homozygous deletion or rearrangements, which would not be susceptible to somatic reversion mutations, as well as BRCA1 hypermethylation, and RAD51C/D mutations. Research Funding: Clovis Oncology, Inc.
Clinical • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset)
|
BRCA1 mutation • HRD • RAD51C mutation • BRCA mutation • BRCA deletion • BRCA1 hypermethylation
|
Rubraca (rucaparib)
almost2years
Comparison of BRCA versus non-BRCA germline mutations and associated somatic mutation profiles in patients with unselected breast cancer. (PubMed, Aging (Albany NY))
By investigating all breast and ovarian cancer-related genes listed in the US genetic guidelines, we identified 15 cancer susceptibility genes frequently mutated in the germline of our population and must be included in cancer predisposition screening. Our study contributed a better understanding of the tumor characteristics of patients with LP/P germline mutations.
Clinical • Journal • BRCA Biomarker
|
TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • MUTYH (MutY homolog)
|
BRCA1 mutation • BRCA2 mutation • PALB2 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation
almost2years
The contribution of germline predisposition gene mutations to clinical subtypes of invasive breast cancer from a clinical genetic testing cohort. (PubMed, J Natl Cancer Inst)
Germline mutations in hereditary cancer panel genes confer subtype-specific risks of breast cancer. Combined tumor subtype, age at breast cancer diagnosis, and family history of breast and/or ovarian cancer information provides refined categorical estimates of mutation prevalence for women considering genetic testing.
Clinical • Journal • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRCA2 mutation • HER-2 mutation • ATM mutation • PALB2 mutation • RAD51D mutation • CHEK2 mutation • RAD51C mutation • BARD1 mutation
almost2years
TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)
P2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: May 2020 --> May 2021
Clinical • Trial primary completion date • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • RAD50 (RAD50 Double Strand Break Repair Protein) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCG (FA Complementation Group G) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
|
RAD51D mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • FANCF mutation • RAD50 mutation • FANCG mutation • FANCI mutation • FANCM mutation • NBN mutation
|
Rubraca (rucaparib)
2years
Postprogression outcomes in patients with ovarian carcinoma associated with a mutation in a non-BRCA homologous recombination repair gene receiving rucaparib maintenance treatment: Results from the phase III study ARIEL3 (SGO 2020)
Although the number of patients in this subgroup was small, rucaparib improved the clinically meaningful endpoints CFI, TFST, PFS2, and TSST versus placebo in patients with platinum-sensitive, recurrent ovarian cancer harboring a non-BRCA HRR gene mutation. Mutations in a subset of HRR genes, such as RAD51C/D, may confer greater sensitivity to PARP inhibitor treatment.
Clinical • P3 data • BRCA Biomarker • PARP Biomarker
|
RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset)
|
BRIP1 mutation • RAD51D mutation • RAD51C mutation
|
Rubraca (rucaparib)
2years
NEO: A Study of Olaparib Prior to Surgery and Chemotherapy in Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov)
P2, N=71, Recruiting, University Health Network, Toronto | Trial completion date: Jun 2020 --> Dec 2021 | Trial primary completion date: Dec 2019 --> Jun 2021
Clinical • Trial completion date • Trial primary completion date • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MUC16 (Mucin 16, Cell Surface Associated) • BARD1 (BRCA1 Associated RING Domain 1) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • FANCM (FA Complementation Group M) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
|
BRCA1 mutation • BRCA2 mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • FANCM mutation • MUC16 expression • PPM1D mutation • RAD51 mutation
|
Lynparza (olaparib)
2years
A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency (clinicaltrials.gov)
P2, N=50, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting
Clinical • Enrollment closed
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA1 mutation • BRCA2 mutation • ATM mutation • PALB2 mutation • MYC amplification • CCNE1 amplification • FBXW7 mutation • RAD51D mutation • RAD51C mutation • RAD51 mutation
|
prexasertib (LY2606368)
over2years
PREVALENCE OF BRCA1/2 MUTATION AND ALTERATIONS OF HOMOLOGOUS RECOMBINATION DEFICIENCY (HRD) IN UTERINE LEIOMYOSARCOMA: A RETROSPECTIVE, MONOCENTRIC STUDY (IGCS 2019)
Final results could open novel perspectives terms of disease pathogenesis, and potential use of target based drugs (e.g.PARP inhibitors).
Retrospective data • BRCA Biomarker • PARP Biomarker
|
TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RAD51C (RAD51 paralog C)
|
TP53 mutation • BRCA1 mutation • BRCA2 mutation • HRD • RAD51C mutation
over2years
REFERRAL PATTERNS AND UPTAKE OF RISK REDUCING SURGERY FOR NON-BRCA GENES ASSOCIATED WITH INCREASED RISK OF EPITHELIAL OVARIAN CANCER (IGCS 2019)
Two-thirds of patients with non- BRCA genes associated with increased risk of ovarian cancer were referred to gynecologic oncologists, with a 48% of uptake or RRS.
BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BRCA (Breast cancer early onset) • EPCAM (Epithelial cell adhesion molecule)
|
BRIP1 mutation • MSH2 mutation • RAD51C mutation • MLH1 mutation • BRCA mutation • PMS2 mutation
over2years
Stand up to Cancer: MAGENTA (Making Genetic Testing Accessible) (clinicaltrials.gov)
P=N/A, N=3000, Not yet recruiting, M.D. Anderson Cancer Center
BRCA Biomarker
|
ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
|
BRCA1 mutation • BRCA2 mutation • PALB2 mutation • BRIP1 mutation • RAD51D mutation • MSH2 mutation • RAD51C mutation • BARD1 mutation • MLH1 mutation • PMS2 mutation • RAD51 mutation