ArticleAmerican journal of human genetics2016
Biallelic BRCA2 Mutations Shape the Somatic Mutational Landscape of Aggressive Prostate Tumors.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Pooled it
- A systematic review of the prevalence of DNA damage response gene mutations in prostate cancer.International journal of oncology · 2019Pooled it
- Complex Relationships Between Homologous Recombination Deficiency (HRD) Score and Mutational Status of Homologous Recombination Repair (HRR) Genes in Prostate Carcinomas.International journal of molecular sciences · 2025Article
- Therapeutic implications of homologous repair deficiency testing in patients with prostate cancer (Part 2 of 2).Prostate cancer and prostatic diseases · 2025Review
- Immunoprevention of non-viral cancers: challenges and strategies for early intervention.Cancer cell international · 2025Review
- Frequent CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression.NPJ precision oncology · 2024Article
- Patient Assessment and Therapy Planning Based on Homologous Recombination Repair Deficiency.Genomics, proteomics & bioinformatics · 2023Review
- Severe hypercalcaemia in metastatic prostate cancer with biallelic BRCA2 mutations and lytic bone lesions.BMJ case reports · 2023Article
- Phosphorylation status of MUS81 is a modifier of Olaparib sensitivity in BRCA2-deficient cells.Nucleic acids research · 2023Article
- Genomic Profiling of Prostate Cancer: An Updated Review.The world journal of men's health · 2022Review
- The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer.NPJ precision oncology · 2022Article
- A unified haplotype-based method for accurate and comprehensive variant calling.Nature biotechnology · 2021Article
- A subset of lung cancer cases shows robust signs of homologous recombination deficiency associated genomic mutational signatures.NPJ precision oncology · 2021Article
- Detection of Molecular Signatures of Homologous Recombination Deficiency in Prostate Cancer with or without BRCA1/2 Mutations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria.International journal of cancer · 2019Article
- Differential Response to Olaparib Treatment Among Men with Metastatic Castration-resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations.European urology · 2019Observational
- Role of BRCA Mutations in Cancer Treatment with Poly(ADP-ribose) Polymerase (PARP) Inhibitors.Cancers · 2018Review
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- Mutations in BRCA2 and taxane resistance in prostate cancer.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
To identify clinically important molecular subtypes of prostate cancer (PCa), we characterized the somatic landscape of aggressive tumors via deep, whole-genome sequencing. In our discovery set of ten tumor/normal subject pairs with Gleason scores of 8-10 at diagnosis, coordinated analysis of germline and somatic variants, including single-nucleotide variants, indels, and structural variants, revealed biallelic BRCA2 disruptions in a subset of samples. Compared to the other samples, the PCa BRCA2-deficient tumors exhibited a complex and highly specific mutation signature, featuring a 2.88-fold increased somatic mutation rate, depletion of context-specific C>T substitutions, and an enrichment for deletions, especially those longer than 10 bp. We next performed a BRCA2 deficiency-targeted reanalysis of 150 metastatic PCa tumors, and each of the 18 BRCA2-mutated samples recapitulated the BRCA2 deficiency-associated mutation signature, underscoring the potent influence of these lesions on somatic mutagenesis and tumor evolution. Among all 21 individuals with BRCA2-deficient tumors, only about half carried deleterious germline alleles. Importantly, the somatic mutation signature in tumors with one germline and one somatic risk allele was indistinguishable from those with purely somatic mutations. Our observations clearly demonstrate that BRCA2-disrupted tumors represent a unique and clinically relevant molecular subtype of aggressive PCa, highlighting both the promise and utility of this mutation signature as a prognostic and treatment-selection biomarker. Further, any test designed to leverage BRCA2 status as a biomarker for PCa must consider both germline and somatic mutations and all types of deleterious mutations.
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Registered trials
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