2024/11/20 by Marc Williams, Michael Oliphant, Vinci Au +22 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #BRCA gene mutations in cancer #Cancer Genomics and Diagnostics #Genetic factors in colorectal cancer
paper · doi:10.1038/s41588-024-01988-0
openalex publication_date 2024/11/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
The prevalence and nature of somatic copy number alterations (CNAs) in breast epithelium and their role in tumor initiation and evolution remain poorly understood. Using single-cell DNA sequencing (49,238 cells) of epithelium from BRCA1 and BRCA2 carriers or wild-type individuals, we identified recurrent CNAs (for example, 1q-gain and 7q, 10q, 16q and 22q-loss) that are present in a rare population of cells across almost all samples (n = 28). In BRCA1/BRCA2 carriers, these occur before loss of heterozygosity (LOH) of wild-type alleles. These CNAs, common in malignant tumors, are enriched in luminal cells but absent in basal myoepithelial cells. Allele-specific analysis of prevalent CNAs reveals that they arose by independent mutational events, consistent with convergent evolution. BRCA1/BRCA2 carriers contained a small percentage of cells with extreme aneuploidy, featuring loss of TP53, BRCA1/BRCA2 LOH and multiple breast cancer-associated CNAs. Our findings suggest that CNAs arising in normal luminal breast epithelium are precursors to clonally expanded tumor genomes.