News - FANCA mutation

23d

NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)

P2, N=51, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=112 --> 51 | Trial completion date: Mar 2027 --> Dec 2027 | Recruiting --> Suspended | Trial primary completion date: Mar 2024 --> Dec 2024

23 days ago

Enrollment change • Trial completion date • Trial suspension • Trial primary completion date • Pan tumor

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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) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • ARID2 (AT-Rich Interaction Domain 2) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)

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HER-2 positive • HER-2 amplification • DDR • PBRM1 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • NBN mutation • DRD

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Zejula (niraparib) • Jemperli (dostarlimab-gxly)

23d

ARIANES: Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors (clinicaltrials.gov)

P2, N=130, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=1000 --> 130 | Trial primary completion date: Apr 2024 --> Dec 2024

23 days ago

Enrollment change • Trial primary completion date • Pan tumor

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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) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • IL2 (Interleukin 2) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)

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DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • NBN mutation • DRD

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Tecentriq (atezolizumab) • Rubraca (rucaparib)

2ms

Genomic drivers in craniopharyngiomas: Analysis of the AACR project GENIE database. (PubMed, Childs Nerv Syst)

CTNNB1 mutations account for a large proportion of somatic mutations in craniopharyngiomas. Identification of specific point mutations and secondary drivers may advance development of novel craniopharyngioma preclinical models for targeted therapy testing.

2 months ago

Journal

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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • FANCA (FA Complementation Group A) • ARID1B (AT-Rich Interaction Domain 1B)

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BRAF mutation • HER-2 mutation • ATM mutation • CTNNB1 mutation • FANCA mutation • BLM mutation

2ms

Epithelioid hemangioendothelioma (EHE) with WWTR1::TFE3 gene fusion, a novel fusion variant. (PubMed, Genes Chromosomes Cancer)

Overall, we describe a novel gene fusion in EHE with a hybrid histological appearance between the two major genetic subtypes of EHE. Further cases of this very rare subtype of EHE will need to be identified to fully elucidate the clinical and pathological characteristics of this unusual subtype of EHE.

2 months ago

Journal

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FANCA (FA Complementation Group A) • YAP1 (Yes associated protein 1) • TFE3 • WWTR1 (WW Domain Containing Transcription Regulator 1) • CAMTA1 (Calmodulin Binding Transcription Activator 1)

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FANCA mutation • TFE3 fusion

2ms

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, Active, not recruiting, Shadia Jalal, MD | Trial completion date: Nov 2024 --> Jul 2024 | Trial primary completion date: Nov 2023 --> Feb 2023

2 months ago

Trial completion date • Trial primary completion date • Metastases

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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) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)

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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • NBN mutation

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Zejula (niraparib)

2ms

Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan. (PubMed, J Biomed Sci)

Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHRmut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.

2 months ago

Clinical • Clinical data • Journal • BRCA Biomarker

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • FANCC (FA Complementation Group C)

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BRCA1 mutation • ATM mutation • PALB2 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • FANCA mutation • BLM mutation • NBN mutation

2ms

A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)

P2, N=5, Terminated, Memorial Sloan Kettering Cancer Center | Completed --> Terminated; Due to low accrual

2 months ago

Trial termination • Metastases

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • 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 • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab)

2ms

TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)

P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting

2 months ago

Enrollment closed

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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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)

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CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • FANCF mutation • NBN mutation • FANCG mutation • FANCI mutation • FANCM mutation

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Rubraca (rucaparib)

2ms

Tissue genomic profiling of pleural mesothelioma patients treated with immunotherapy: Unraveling genetic alterations and complexity (ELCC 2024)

Conclusions Our study did not identify predictive or prognostic factors for IO outcomes in unresectable PM, emphasizing the complexity and heterogeneity of PM. Further research with larger cohorts is crucial to unveil biomarkers in this setting.

2 months ago

Clinical • Tumor mutational burden • IO biomarker

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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BAP1 (BRCA1 Associated Protein 1) • NF2 (Neurofibromin 2) • FANCA (FA Complementation Group A)

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PIK3CA mutation • BAP1 mutation • NF2 mutation • FANCA mutation

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FoundationOne® CDx • OmniSeq INSIGHT

3ms

Genotype-histotype-phenotype correlations in hyperinsulinemic hypoglycemia. (PubMed, Histol Histopathol)

The genetic cause is unknown in most cases. The diagnosis of HH, as defined by genetic, histological, and phenotypic features, has important implications for patient management and outcome.

3 months ago

Review • Journal

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MEN1 (Menin 1)

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FANCA mutation

3ms

KNIGHTS: High-Risk Metachronous Oligometastatic Prostate Cancer Trial (clinicaltrials.gov)

P2, N=88, Not yet recruiting, University of Maryland, Baltimore

3 months ago

New P2 trial • Metastases

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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • RAD54L (DNA Repair And Recombination Protein RAD54)

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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • FANCA mutation

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Zejula (niraparib) • abiraterone acetate • prednisone

3ms

OPTIMUM: Olaparib With or Without Durvalumab for DDR Gene Mutated Biliary Tract Cancer Following Platinum-based Chemotherapy (clinicaltrials.gov)

P2, N=62, Recruiting, Asan Medical Center | Trial completion date: Oct 2024 --> Dec 2025 | Trial primary completion date: Oct 2023 --> Dec 2024

3 months ago

Trial completion date • Trial primary completion date • Metastases

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • POLE (DNA Polymerase Epsilon) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCD2 (FA Complementation Group D2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)

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ATM mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • FANCA mutation • RAD50 mutation • BARD1 mutation • BLM mutation • NBN mutation

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Lynparza (olaparib) • Imfinzi (durvalumab)

4ms

Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)

P1, N=30, Suspended, National Cancer Institute (NCI) | Initiation date: Oct 2023 --> Jul 2023

4 months ago

Trial initiation date

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation

4ms

Germline mutations in pediatric cancer cohort with mixed-ancestry Mexicans. (PubMed, Mol Genet Genomic Med)

This report identifies potential genetic risk factors and provides a better understanding of the underlying mechanisms of childhood cancer in this population.

4 months ago

Journal

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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • MUTYH (MutY homolog) • DICER1 (Dicer 1 Ribonuclease III)

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CDKN2A mutation • CHEK2 mutation • FANCA mutation

4ms

Germline mutations in patients with metastatic prostate cancer: A prospective cohort study in South Korea (KCSG GU20-19). (ASCO-GU 2024)

The prevalence of pathogenic germline mutations among unselected Korean patients with metastatic prostate cancer was 12.0 %. Germline mutation prevalence in this cohort was comparable to previous reported results. This study provides the framework for the development of preventive and treatment strategies based on hereditary genetic factors for prostate cancer in the Korean population.P, pathogenic; LP, likely pathogenic.

4 months ago

Clinical • BRCA Biomarker • Metastases

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BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • SLFN11 (Schlafen Family Member 11) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • MRE11A (MRE11 homolog, double strand break repair nuclease) • FANCD2 (FA Complementation Group D2)

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BRCA2 mutation • ATM mutation • FANCA mutation • BLM mutation

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SOLIDaccuTest DNA

5ms

Novel Gene Mutations Associated with Disease-Free Survival in Elderly Patients with Acute Myeloid Leukemia Receiving First-Line Induction-Consolidation with or without Azacitidine Post-Remission Treatment (ASH 2023)

HLA gene mutations are not usually investigated for diagnostic or prognostic purposes in AML. The extensive 350-gene panel used in this study included HLA genes and has revealed a possible favorable role of HLA-A polimorphisms for the prognosis of elderly patients with AML undergoing intensive chemotherapy. Further specific HLA NGS analyses are undergoing to determine whether this concerns genuine somatic mutations.

5 months ago

Clinical

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NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • FANCA (FA Complementation Group A)

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DNMT3A mutation • TET2 mutation • FANCA mutation

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azacitidine

5ms

Loss of chromosome 9p21 is associated with a poor prognosis in adenosquamous carcinoma of the pancreas. (PubMed, Precis Clin Med)

The mutation rates of ACVR2A (6.25% vs 0%), FANCA (6.25% vs 0%), RBM10 (6.25% vs 0%), and SPTA1 (8.33% vs 1.02%) were significantly higher in ASCP than in PDAC. In conclusion, we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP, which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP.

5 months ago

Journal

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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • SMAD4 (SMAD family member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FANCA (FA Complementation Group A) • RBM10 (RNA Binding Motif Protein 10) • FAT3 (FAT Atypical Cadherin 3) • SPTA1 (Spectrin Alpha) • ACVR2A (Activin A Receptor Type 2A) • SFTPA1 (Surfactant Protein A1)

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CDKN2A deletion • FANCA mutation • FAT3 mutation

5ms

Mutation spectrum, expression profiling, and prognosis evaluation of Fanconi anemia signaling pathway genes for 4259 patients with myelodysplastic syndromes or acute myeloid leukemia. (PubMed, BMC Med Genomics)

This investigation facilitates a deeper understanding of the functional links between FA and MDS/AML.

5 months ago

Journal

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FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • FANCI (FA Complementation Group I)

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FANCA mutation • RAD51 mutation

5ms

Molecular profiling and prognostic analysis in Chinese cholangiocarcinoma: an observational, retrospective single-center study. (PubMed, Invest New Drugs)

Furthermore, mutations in APC, DAXX, FANCA, LTK, MAP2K4, and NOTCH1 were associated with a poor prognosis (P < 0.05). This study provides an overview of genetic alterations in Chinese patients with CCA, which will provide novel potential biomarkers for the diagnosis of CCA and may guide targeted therapeutic strategies for Chinese patients with CCA.

5 months ago

Retrospective data • Journal

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TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • AXL (AXL Receptor Tyrosine Kinase) • SMAD4 (SMAD family member 4) • FANCA (FA Complementation Group A) • NOTCH3 (Notch Receptor 3) • DAXX (Death-domain associated protein) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4)

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TP53 mutation • APC mutation • SMAD4 mutation • FANCA mutation • NOTCH3 mutation

5ms

Elucidating the transcriptomic landscape of metastatic pediatric Medulloblastoma (SNO 2023)

Work is currently being done to profile the epigenome of LMD by correlating transcriptomic data with active chromatin markers such as H3K27ac and H3K4me1. Through these approaches, we aim to elucidate the genetic dependencies of metastatic Medulloblastoma that will help for targeted therapies.

5 months ago

Clinical • Metastases

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SLC17A9 (Solute Carrier Family 17 Member 9)

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FANCA mutation

5ms

Metastatic Prostate cancer (mPCa) and Homologous Recombination Deficiency (HRD) in daily practice: experience of 6 years in a tertiary hospital. (EMUC 2023)

mPCa without HRD N =132 mPCa with HRD N=12 Median age - years (IQR) 65.0 (59.0-71.0) 57.5 (53.3-71.3)* De novo mHSPC, n (%) Bones (%) Lymph nodes (%) Liver (%) Other (%) 55 (41.7) 100 (75.8) 79 (59.8) 10 (7.6) 24 (18.2) 6 (50.0) 11 (91.7) 8 (66.7) - - High volume disease, n (%) 42 (31.8) 5 (41.7) ISUP Grade Group, n (%) 1 2 3 4 5 Missing 8 (2.3) 17 (12.9) 10 (7.6) 27 (20.5) 56 (42.4) 11 (8.3) - 1 (8.3) 1 (8.3) 3 (25.0) 6 (50.0) Neuroendocrine Histology, n (%) 3 (2.3) 1 (8.3) Radical Surgery, n (%) 44 (33.3) 4 (33.3) Radical radiotherapy, n (%) 75 (56.8) 5 (41.7) Baseline ECOG-PS, n (%) 0 1 2 3 Missing 63 (47.7) 51 (38.6) 11 (8.3) 1 (0.8) 6 (4.5) 3 (25.0) 8 (66.7) - - 1 (8.3) 1st line treatment, n (%) Nover Hormone Agent Docetaxel Other Best Supportive Care 83 (62.9) 38 (28.8) 8 (6.1) 3 (2.3) 6 (50) 6 (50) - - Sample Tissue, n (%) Tumour Peripheral Blood Both 15 (11.4) 16 (12.1) 101 (76.5) 1 (8.3) 5 (42.7) 6 (50.0) DDR mutation, n (%) BRCA2 BRCA1 FANCA ATM 8 (66.7) 2 (16.7) 1 (8.3) 1 (8.3) Deaths, n (%) 64 (48.5) 9 (75.0) *p<0.05...Using different analysis techniques optimize the diagnosis of HRD. BRCA mutations confer a detrimental impact on survival.

5 months ago

Clinical • BRCA Biomarker • Metastases

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • FANCA (FA Complementation Group A)

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BRCA1 mutation • HRD • ATM mutation • FANCA mutation • BRCA mutation

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docetaxel

6ms

Unique molecular signatures of germline mutations in low expression of human epidermal growth factor receptor 2 (HER2) breast cancer (SABCS 2023)

HER2-low BC patients have distinct germline mutational signatures and differential clinical outcomes under neoadjuvant systemic therapy. These results have provided additional evidence that HER2-low patients comprise a fourth subtype of BC that needs to be accounted for separately in terms of clinical treatment and outcome reporting.

6 months ago

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) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • ERCC1 (Excision repair cross-complementation group 1) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MUTYH (MutY homolog) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FLCN (Folliculin) • FANCD2 (FA Complementation Group D2) • RECQL4( RecQ Like Helicase 4) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • RAD54B (RAD54 Homolog B)

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BRCA1 mutation • EGFR mutation • HER-2 overexpression • HER-2 mutation • HER-2 expression • ATM mutation • PALB2 mutation • MSH2 mutation • RAD51C mutation • FANCA mutation • PMS2 mutation • FANCI mutation • FANCM mutation • RAD51 mutation • RECQL4 mutation

7ms

Testing the Sequential Combination of the Anti-cancer Drugs Olaparib Followed by Adavosertib (AZD1775) in Patients With Advanced Solid Tumors With Selected Mutations and PARP Resistance, STAR Study (clinicaltrials.gov)

P1, N=16, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Sep 2024

7 months ago

Trial completion date • Metastases

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CD4 (CD4 Molecule)

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BRCA2 mutation • BRCA1 mutation • CCNE1 amplification • BRIP1 mutation • FANCA mutation

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Lynparza (olaparib) • adavosertib (AZD1775)

7ms

Exceptional Response to Olaparib: A Case Report of Metastatic Esophageal Squamous Cell Carcinoma in a Patient With Fanconi Anemia, Germline FANCA Mutation, and Somatic BRCA2 Mutations. (PubMed, JCO Precis Oncol)

No abstract available

7 months ago

Journal • BRCA Biomarker • PARP Biomarker • Metastases

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BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A)

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BRCA2 mutation • FANCA mutation

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Lynparza (olaparib)

7ms

Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)

P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

7 months ago

Trial suspension

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation

7ms

FANCA deficiency promotes leukaemic progression by allowing the emergence of cells carrying oncogenic driver mutations. (PubMed, Oncogene)

Collectively, our observations indicate that loss of the FANC pathway, known to control genetic instability, fosters the expansion of leukaemic cells carrying oncogenic mutations rather than mutation formation. FANCA loss may contribute to this leukaemogenic progression by reprogramming transcriptomic landscape of the cells.

7 months ago

Journal • Tumor mutational burden

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TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FANCA (FA Complementation Group A) • MDM4 (The mouse double minute 4) • SPI1 (Spi-1 Proto-Oncogene)

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KIT mutation • FANCA mutation

8ms

The Spectrum of Germline Nucleotide Variants in Gastric Cancer Patients in the Kyrgyz Republic. (PubMed, Curr Issues Mol Biol)

The use of recognized criteria (NCCN, Gastric Cancer, Version 2.2022) would increase the number of identified genetic variants in hereditary GC-associated genes. Further research is required to determine the clinical relevance of the genetic variants identified in the current study.

8 months ago

Journal • BRCA Biomarker

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TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • SMAD4 (SMAD family member 4) • CDH1 (Cadherin 1) • FANCA (FA Complementation Group A) • POLD1 (DNA Polymerase Delta 1) • FANCD2 (FA Complementation Group D2)

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PALB2 mutation • FANCA mutation

8ms

A comprehensive analysis of Fanconi anemia genes in Chinese patients with high-risk hereditary breast cancer. (PubMed, J Cancer Res Clin Oncol)

This study comprehensively estimated the prevalence, clinicopathological characteristics, prognosis and risk of BC associated with deleterious variants in FA genes in Chinese high-risk hereditary BC patients. It enriches our understanding of the role of FA genes with BC.

8 months ago

Journal • BRCA Biomarker

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ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCB (FA Complementation Group B)

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BRIP1 mutation • FANCA mutation • FANCM mutation

8ms

Clinical and genetic characteristics in lymphoma patients with a second solid malignancy. (PubMed, Front Oncol)

In summary, comprehensive study of the clinical and genetic features of patients with multiple primary malignancies may improve diagnosis and treatment in the future. Mutations in FANC genes might be a predisposition to tumorigenesis of lymphoma patients with a second solid malignancy.

8 months ago

Journal

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BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCG (FA Complementation Group G)

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FANCA mutation • FANCF mutation • FANCG mutation • FANCI mutation

9ms

PARPiPANC: A multicentric, single arm, phase II assessing niraparib as first line therapy for patients with metastatic homologous repair-deficient pancreatic cancer (ESMO 2023)

Correlative studies include documentation of HR alteration at time of progression on optional de novo tumor biopsy as well as assessment of predictive value for niraparib resistance of existing or new variants using liquid biopsies. To date, 4 French hospitals are participating.

9 months ago

Clinical • P2 data • BRCA Biomarker • PARP Biomarker • Metastases

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCD2 (FA Complementation Group D2)

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BRCA2 mutation • BRCA1 mutation • BRIP1 mutation • FANCA mutation • NBN mutation

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Zejula (niraparib)

9ms

Homologous recombination repair (HRR) gene mutation: A novel biomarker for precision genomics testing in advanced lung cancer (ESMO 2023)

Table: 1429P Conclusions The HRR gene mutation in advanced lung cancer was independent of the predictors for immunotherapy response (TMB, MSI and PD-L1 biomarkers). Further clinical trials are needed to assess the efficacy of combining poly ADP ribose polymerase (PARP) inhibitors with immunotherapy in the future.

9 months ago

Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker • Metastases

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TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)

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BRCA2 mutation • ATM mutation • ARID1A mutation • CDK12 mutation • BRIP1 mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • BRCA mutation • CHEK1 mutation • CHEK1 expression

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FoundationOne® CDx

9ms

HRR Gene Mutations- A New Biomarker for Precision Genomics Based Testing in Metastatic Lung Cancer (IASLC-WCLC 2023)

The emphasis on precision genomics-based targeted therapy in metastatic lung cancer is evolving rapidly and the addition of new HRR genes-based biomarker testing in lung cancer promotes opportunity for further clinical trials to assess the efficacy of combining PARP inhibitors with Immunotherapy in the future.

9 months ago

Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker • Metastases

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PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IL1R1 (Interleukin 1 receptor, type I) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)

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PD-L1 expression • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • ATM mutation • ARID1A mutation • PD-L1 negative • PALB2 mutation • CDK12 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • BRCA mutation • CHEK1 mutation • FANCG mutation • RAD51 mutation • CHEK1 expression

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FoundationOne® CDx

9ms

High throughput single cell long-read sequencing analyses of same-cell genotypes and phenotypes in human tumors. (PubMed, Nat Commun)

Transcriptome-wide mutation analyses identify many cell-type-specific mutations including VEGFA mutations in tumor cells and HLA-A mutations in immune cells, highlighting the critical roles of different mutant populations in tumors. Together, scNanoGPS facilitates applications of single-cell long-read sequencing technologies.

9 months ago

Journal

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VEGFA (Vascular endothelial growth factor A) • CCL3 (C-C Motif Chemokine Ligand 3)

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FANCA mutation • VEGFA mutation

9ms

Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)

P1, N=30, Recruiting, National Cancer Institute (NCI) | Initiation date: Jul 2023 --> Oct 2023

9 months ago

Trial initiation date

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation

9ms

A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)

P2, N=5, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> Jul 2023 | Trial primary completion date: Feb 2024 --> Jul 2023

9 months ago

Trial completion • Trial completion date • Trial primary completion date • Metastases

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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) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • 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 • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • FANCA deletion

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Lynparza (olaparib) • Imfinzi (durvalumab)

10ms

Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)

P1, N=30, Recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2023 --> Jul 2023

10 months ago

Trial initiation date

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation

10ms

Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer. (PubMed, Sci Rep)

In conclusion, TP53 and PIK3CA mutations, as well as a higher ctDNA fraction, were associated with worse PFS with trastuzumab and cytotoxic chemotherapy. The enrichment of HRD-related gene mutations and newly detected variants in ctDNA may be related to resistance to treatment.

10 months ago

Journal • BRCA Biomarker • Circulating tumor DNA • Metastases

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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein)

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TP53 mutation • PIK3CA mutation • HRD • BRIP1 mutation • ERBB3 mutation • FANCA mutation • RAD50 mutation

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Herceptin (trastuzumab) • DA 3111 (trastuzumab biosimilar)

12ms

Extended molecular profiling in patients with biliary tract cancers: Impact of the BRCAness phenotype in patients management (ESMO-GI 2023)

In our retrospective series, a significant proportion of patients with hereditary forms linked to BRCA1 and BRCA2 was found. The implementation of a wider molecular characterization is important not only for therapeutical implication but also for identifying any potential carriers of somatic alteration that could refer patients to a specific genetic counseling. BRCAness phenotype, moreover, seems to identify patients with a better prognosis, thus shedding light on its clinical significance.

12 months ago

Clinical • BRCA Biomarker

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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

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BRCA1 mutation • ARID1A mutation • BAP1 mutation • FANCA mutation

12ms

Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)

P1, N=30, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

12 months ago

Enrollment open

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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation

12ms

Targeting germline or somatic DNA repair defects (beyond BRCA) in pancreatic cancer with niraparib: A phase II study (NIRA-PANC). (ASCO 2023)

In previously treated pts with locally advanced and metastatic PC harboring DNA repair defects, niraparib monotherapy yielded a 6-month PFS rate of 40%, median PFS of 4.4 months, and median OS of 9.1 months. Clinical trial information: NCT03553004. >

12 months ago

P2 data • BRCA Biomarker • PARP Biomarker

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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) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCD2 (FA Complementation Group D2) • FANCG (FA Complementation Group G) • RPA1 (Replication Protein A1) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)

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BRCA2 mutation • BRCA1 mutation • ATM mutation • CHEK2 mutation • BRIP1 mutation • FANCA mutation • RAD51B mutation • BRCA mutation • NBN mutation • FANCG mutation

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Zejula (niraparib)