ArticlePLoS genetics2012
Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 2 of them syntheses that pooled it.
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Who cites it
127 citing papers in PubMed, 2 syntheses or guidelines pooled it, 211 citations in OpenAlex.
- A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Pooled it
- Analysis of a RECQL splicing mutation, c.1667_1667+3delAGTA, in breast cancer patients and controls from Central Europe.Familial cancer · 2017Pooled it
- Targeted Sequencing of the Mitochondrial Genome of Women at High Risk of Breast Cancer without Detectable Mutations in BRCA1/2.PloS one · 2015Trial
- The effects of soy supplementation on gene expression in breast cancer: a randomized placebo-controlled study.Journal of the National Cancer Institute · 2014Trial
- Recent Advances in Genetic Testing and Clinical Management of Hereditary Breast and Ovarian Cancer (HBOC) in India.Cancer medicine · 2026Review
- Investigating the contribution of rare non-coding variants in BRCA1, BRCA2 and PALB2 to hereditary breast cancer.NPJ breast cancer · 2026Article
- PathogenicCurrent issues in molecular biology · 2025Article
- Comprehensive RAD51C ovarian cancer variant analysis uncouples homologous recombination and replicative functions.Nature communications · 2025Article
- Distinct developmental outcomes in DNA repair-deficient FANCC c.67delG mutant and FANCCCell death and differentiation · 2025Article
- Understanding how gene-disease relationships can impact clinical utility: adaptations and challenges in hereditary cancer testing.Genome medicine · 2025Article
- Detection rates of multigene panel and exome testing in patients with previous negative BRCA1/2 results.Familial cancer · 2025Article
- Assessment of candidate high-grade serous ovarian carcinoma predisposition genes through integrated germline and tumour sequencing.NPJ genomic medicine · 2025Article
- Increased frequency of clonal hematopoiesis of indeterminate potential in Bloom syndrome probands and carriers.Haematologica · 2025Article
- Asymptomatic Bloom syndrome diagnosed by chance in a patient with breast cancer.Familial cancer · 2024Article
- Germline DNA Damage Repair Gene Alterations in Patients with Metachronous Breast and Colorectal Cancer.International journal of molecular sciences · 2024Article
- STIL facilitates the development and malignant progression of triple-negative breast cancer through activation of Fanconi anemia pathway via interacting with KLF16.Translational oncology · 2024Article
- First report of familial mixed phenotype acute leukemia: shared clinical characteristics, Philadelphia translocation, and germline variants.International journal of hematology · 2024Article
- Genomic Alterations Correlated to Trastuzumab Resistance and Clinical Outcomes in HER2+/HR- Breast Cancers of Patients Living in Northwestern China.Journal of Cancer · 2024Article
- "I don't need any more unknowns hanging over my head": Views of patients with cancer on variants of uncertain significance and low/moderate risk results from genomic sequencing.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- A comprehensive analysis of Fanconi anemia genes in Chinese patients with high-risk hereditary breast cancer.Journal of cancer research and clinical oncology · 2023Article
67 more citing papers are in PubMed but not listed here.
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17 authors at 3 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for the majority of families with a multi-generational breast cancer predisposition is unknown. In this study, we used whole-exome sequencing of thirty-three individuals from 15 breast cancer families to identify potential predisposing genes. Our analysis identified families with heterozygous, deleterious mutations in the DNA repair genes FANCC and BLM, which are responsible for the autosomal recessive disorders Fanconi Anemia and Bloom syndrome. In total, screening of all exons in these genes in 438 breast cancer families identified three with truncating mutations in FANCC and two with truncating mutations in BLM. Additional screening of FANCC mutation hotspot exons identified one pathogenic mutation among an additional 957 breast cancer families. Importantly, none of the deleterious mutations were identified among 464 healthy controls and are not reported in the 1,000 Genomes data. Given the rarity of Fanconi Anemia and Bloom syndrome disorders among Caucasian populations, the finding of multiple deleterious mutations in these critical DNA repair genes among high-risk breast cancer families is intriguing and suggestive of a predisposing role. Our data demonstrate the utility of intra-family exome-sequencing approaches to uncover cancer predisposition genes, but highlight the major challenge of definitively validating candidates where the incidence of sporadic disease is high, germline mutations are not fully penetrant, and individual predisposition genes may only account for a tiny proportion of breast cancer families.
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