ArticleCancer science2024
BRCA1/2 reversion mutations in a pan-cancer cohort.
Article in Cancer science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 15 citations in OpenAlex.
- Focal adhesion kinase inhibitor defactinib enhances olaparib-induced suppression of BRCA-proficient breast cancer cell proliferation.Oncology letters · 2026Article
- A Novel BRCA1 Pathogenic Variant in Tunisian Patient With High Grade Ovarian Cancer: Favorable Therapeutic Response to Olaparib.Cancer reports (Hoboken, N.J.) · 2026Article
- Review
- Dynamic ecosystems of tumor drug resistance mechanisms: from molecular heterogeneity to systemic interventions.Apoptosis : an international journal on programmed cell death · 2026Review
- CDCA7 promotes chemoresistance of drug-tolerant persister cells in breast cancer by upregulating the expression of autophagy-related protein genes.Frontiers in immunology · 2026Article
- From dual inhibition to precision selectivity: the molecular rationale and clinical evolution of next-generation PARP1-selective inhibitors in solid tumors.Frontiers in oncology · 2026Review
- Emergence of BRCA Reversion Mutations in Prostate Cancer Prior to PARP Inhibitor Exposure: Clinical and Therapeutic Implications.Cancer medicine · 2026Article
- Article
- Computer-Aided Drug Design Across Breast Cancer Subtypes: Methods, Applications and Translational Outlook.International journal of molecular sciences · 2025Review
- CG>TG mutation frequency as negative predictor of homologous recombination deficiency in ovarian and breast cancer.Communications biology · 2025Article
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- Article
- Causative Genes of Homologous Recombination Deficiency (HRD)-Related Breast Cancer and Specific Strategies at Present.Current oncology (Toronto, Ont.) · 2025Review
- PARP Inhibitors in Pancreatic Cancer with Homologous Recombination Repair Gene Mutations: A Single-Institution Experience.Cancers · 2024Article
- High likelihood of BRCA2 reversion mutation in pancreatic cancer post-platinum-based chemotherapy: a case study.International cancer conference journal · 2024Article
- BRCA1/2 reversion mutations in a pan-cancer cohort.Cancer science · 2024Article
Corrections and comments
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Authors and funding
23 authors at 9 institutions in 1 country.
Funding
Abstract
Tumor sensitivity to platinum (Pt)-based chemotherapy and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors is increased by homologous recombination deficiency-causing mutations; in particular, reversion mutations cause drug resistance by restoring protein function. Treatment response is predicted by breast cancer susceptibility gene 1/2 (BRCA1/2) mutations; however, BRCA1/2 reversion mutations have not been comprehensively studied in pan-cancer cohorts. We aimed to characterize BRCA1/2 reversion mutations in a large pan-cancer cohort of Japanese patients by retrospectively analyzing sequencing data for BRCA1/2 pathogenic/likely pathogenic mutations in 3738 patients with 32 cancer types. We identified somatic mutations in tumors or circulating cell-free DNA that could restore the ORF of adverse alleles, including reversion mutations. We identified 12 (0.32%) patients with somatic BRCA1 (n = 3) and BRCA2 (n = 9) reversion mutations in breast (n = 4), ovarian/fallopian tube/peritoneal (n = 4), pancreatic (n = 2), prostate (n = 1), and gallbladder (n = 1) cancers. We identified 21 reversion events-BRCA1 (n = 3), BRCA2 (n = 18)-including eight pure deletions, one single-nucleotide variant, six multinucleotide variants, and six deletion-insertions. Seven (33.3%) reversion deletions showed a microhomology length greater than 1 bp, suggesting microhomology-mediated end-join repair. Disease course data were obtained for all patients with reversion events: four patients acquired mutations after PARP-inhibitor treatment failure, two showed somatic reversion mutations after disease progression, following Pt-based treatment, five showed mutations after both treatments, one patient with pancreatic cancer and BRCA1 reversion mutations had no history of either treatment. Although reversion mutations commonly occur in BRCA-associated cancers, our findings suggest that reversion mutations due to Pt-chemotherapy might be correlated with BRCA1/2-mediated tumorigenesis even in non-BRCA-associated histologies.
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Registered trials
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