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    BIOMARKER:

    BRCA2 biallelic inactivation

    i
    Other names: BRCA2, BRCC2, FACD, FAD, FAD1, FANCD, FANCD1, Breast cancer 2, early onset
    Entrez ID:
    675
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    over2years
    Fanconi Anemia caused by biallelic inactivation of BRCA2 can present with an atypical cancer phenotype in adulthood. (PubMed, Clin Genet)
    Our data highlight the striking phenotypic differences which can be observed within FA-D1 families and expands the clinical spectrum of FA-D1 to include adult presentation with a constellation of solid tumors not previously thought of as characteristic of Fanconi Anemia. Early recognition of this syndrome in a family could prevent further morbidity and mortality by implementation of hereditary breast and ovarian cancer screening and treatment strategies for heterozygous family members.
    Journal
    |
    BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A)
    |
    BRCA2 biallelic inactivation
    almost3years
    Docetaxel and Carboplatin in Treating Patients With Metastatic, Castration Resistant Prostate Cancer Containing Inactivated Genes in the BRCA 1/2 Pathway (clinicaltrials.gov)
    P2; N=14; Completed; Sponsor: University of Washington; Active, not recruiting --> Completed; Trial completion date: Dec 2021 --> Sep 2021; Trial primary completion date: Dec 2021 --> Sep 2021
    Trial completion date • Trial primary completion date • Trial completion
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    |
    PALB2 mutation • BRIP1 mutation • BRCA2 biallelic inactivation
    |
    FoundationOne® CDx
    |
    carboplatin • docetaxel
    over3years
    Docetaxel and Carboplatin in Treating Patients With Metastatic, Castration Resistant Prostate Cancer Containing Inactivated Genes in the BRCA 1/2 Pathway (clinicaltrials.gov)
    P2; Recruiting --> Active, not recruiting
    Enrollment closed • Clinical
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    |
    PALB2 mutation • BRIP1 mutation • BRCA2 biallelic inactivation
    |
    FoundationOne® CDx
    |
    carboplatin • docetaxel
    almost4years
    Docetaxel and Carboplatin in Treating Patients With Metastatic, Castration Resistant Prostate Cancer Containing Inactivated Genes in the BRCA 1/2 Pathway (clinicaltrials.gov)
    P2;Phase classification: P=N/A --> P2 | Trial completion date: Jun 2021 --> Dec 2021 | Trial primary completion date: Jun 2021 --> Dec 2021
    Trial completion date • Trial primary completion date • Phase classification • Clinical
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    |
    PALB2 mutation • BRIP1 mutation • BRCA2 biallelic inactivation
    |
    FoundationOne® CDx
    |
    carboplatin • docetaxel
    4years
    Pan-cancer landscape of homologous recombination deficiency. (PubMed, Nat Commun)
    We find that while the specific genetic cause of HRD is cancer type specific, biallelic inactivation is predominantly associated with loss-of-heterozygosity (LOH), with increased contribution of deep deletions in prostate cancer. Our results demonstrate the value of pan-cancer genomics-based HRD testing and its potential diagnostic value for patient stratification towards treatment with e.g. poly ADP-ribose polymerase inhibitors (PARPi).
    Journal • BRCA Biomarker • PARP Biomarker • Pan Tumor
    |
    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)
    |
    HRD • BRCA2 biallelic inactivation
    over4years
    A preclinical trial and molecularly-annotated patient cohort identify predictive biomarkers in homologous recombination deficient pancreatic cancer. (PubMed, Clin Cancer Res)
    In summary, we propose a predictive and prognostic model of gBRCA-mutated PDAC based on HRD genomic hallmarks, Ki67 index, tumour ploidy and transcriptomic subtype.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
    |
    HRD • BRCA2 biallelic inactivation
    |
    cisplatin • Talzenna (talazoparib)
    over4years
    Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer (clinicaltrials.gov)
    P2, N=2, Terminated, University of Washington | N=15 --> 2 | Suspended --> Terminated; Terminated due to slow accrual
    Clinical • Enrollment change • Trial termination
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • FANCA (FA Complementation Group A)
    |
    HRD • ATM mutation • PALB2 mutation • BRCA2 biallelic inactivation
    |
    Lynparza (olaparib)
    over4years
    Docetaxel and Carboplatin in Treating Patients With Metastatic, Castration Resistant Prostate Cancer Containing Inactivated Genes in the BRCA 1/2 Pathway (clinicaltrials.gov)
    P=N/A, N=14, Recruiting, University of Washington | Trial completion date: Dec 2020 --> Jun 2021 | Trial primary completion date: Jun 2020 --> Jun 2021
    Clinical • Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    |
    PALB2 mutation • BRIP1 mutation • BRCA2 biallelic inactivation
    |
    carboplatin • docetaxel
    over4years
    [VIRTUAL] HRDetect as a predictive score of platinum response in advanced PDAC (AACR-II 2020)
    In patients treated with modified FOLFIRINOX(mFFX) (n=111, *includes 2 patients treated with cisplatin/gemcitabine) the response rate in HRDetecthi patients (n=16) was 56% vs 20% in HRDetectlo patients (n=95) p=0.005. There was no difference in response rates according to HRDetect score in patients treated with gemcitabine-nab-paclitaxel; HRDetecthi (n=7) 14.3% vs. HRDetectlo(n=71) 32.8%, p=0.42... In patients with advanced PDAC with high HRDetect scores, response rate to FFX is over 50% and survival is significantly longer compared to patients with PDAC and low HRDetect scores. HRDetect identifies an additional population of patients with non-HRD PDAC who benefit from DNA damaging agents.
    BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C)
    |
    BRCA2 biallelic inactivation
    |
    cisplatin • gemcitabine • albumin-bound paclitaxel
    over4years
    Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer (clinicaltrials.gov)
    P2; N=15; Suspended; Sponsor: University of Washington; Recruiting --> Suspended
    Trial suspension • Clinical
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • FANCA (FA Complementation Group A)
    |
    HRD • ATM mutation • PALB2 mutation • BRCA2 biallelic inactivation
    |
    Lynparza (olaparib)
    over6years
    Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer (clinicaltrials.gov)
    P2; N=15; Not yet recruiting; Sponsor: University of Washington
    New P2 trial • Clinical
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • FANCA (FA Complementation Group A)
    |
    HRD • ATM mutation • PALB2 mutation • BRCA2 biallelic inactivation
    |
    Lynparza (olaparib)