{"doi":"10.1172/jci148113","title":"Single-cell analysis of somatic mutation burden in mammary epithelial cells of pathogenic BRCA1/2 mutation carriers","abstract":"Inherited germline mutations in the breast cancer gene 1 (BRCA1) or BRCA2 genes (herein BRCA1/2) greatly increase the risk of breast and ovarian cancer, presumably by elevating somatic mutational errors as a consequence of deficient DNA repair. However, this has never been directly demonstrated by a comprehensive analysis of the somatic mutational landscape of primary, noncancer, mammary epithelial cells of women diagnosed with pathogenic BRCA1/2 germline mutations. Here, we used an accurate, single-cell whole-genome sequencing approach to first show that telomerized primary mammary epithelial cells heterozygous for a highly penetrant BRCA1 variant displayed a robustly elevated mutation frequency as compared with their isogenic control cells. We then demonstrated a small but statistically significant increase in mutation frequency in mammary epithelial cells isolated from the breast of BRCA1/2 mutation carriers as compared with those obtained from age-matched controls with no genetically increased risk for breast cancer.","journal":"Journal of Clinical Investigation","year":2022,"id":269902,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":273647,"name":"Kristina Brazhnik","orcid":"0000-0002-3077-1952","position":1,"is_corresponding":false},{"id":486421,"name":"Moonsook Lee","orcid":"0000-0002-5895-2114","position":2,"is_corresponding":false},{"id":273651,"name":"Alexander Y. Maslov","orcid":"0000-0001-5402-8891","position":3,"is_corresponding":false},{"id":933164,"name":"Yi Zhang","orcid":"0000-0002-5517-0678","position":4,"is_corresponding":false},{"id":933165,"name":"Zhenqiu Huang","orcid":"0000-0001-5882-2726","position":5,"is_corresponding":false},{"id":933166,"name":"Susan Klugman","orcid":"0000-0001-8775-008X","position":6,"is_corresponding":false},{"id":933540,"name":"Ben H. Park","orcid":null,"position":7,"is_corresponding":false},{"id":133023,"name":"Jan Vijg","orcid":null,"position":8,"is_corresponding":false},{"id":387966,"name":"Cristina Montagna","orcid":"0000-0003-2343-5851","position":9,"is_corresponding":false},{"id":273648,"name":"Shixiang Sun","orcid":"0000-0001-5499-2963","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T00:27:22.602796Z","pmid":"35025760","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}