Prevalence of BRCA1/2 large genomic rearrangements in Chinese women with sporadic triple‐negative or familial breast cancer. Issue 1 (3rd May 2018) - Su, L.
Abstract : The prevalence of BRCA1/2 large genomic rearrangements (LGRs) and their underlying mechanisms have not been fully evaluated in Chinese women with breast cancer. In this study, we determined the prevalence of BRCA1/2 LGRs in 834 patients with familial breast cancer (FBC) and 660 patients with sporadic triple‐negative breast cancer (TNBC) who were negative for BRCA1/2 small‐range mutations using the multiplex ligation‐dependent probe amplification method. We found that 20 index patients (2.4%) in the FBC group carried a BRCA1 or BRCA2 LGR, and the frequencies of BRCA1 and BRCA2 LGRs were 1.6% and 0.8%, respectively. Seven index patients (1.1%) carried a BRCA1 LGR in 660 sporadic TNBC patients, whereas no BRCA2 LGRs were found in these patients. Among the BRCA1/2 LGRs, 48.1% (13/27) were novel, and the breakpoints of the majority of the LGRs were identified. ΨBRCA1 ‐mediated homologous recombination (HR) and Alu‐mediated HR/non‐homologous end‐joining (NHEJ) accounted for 40% and 30% of the BRCA1 LGRs, respectively. Alu‐mediated HR accounted for 71.4% of the BRCA2 LGRs, and the remaining one‐third was generated through Long interspersed nuclear elements (LINE)‐mediated NHEJ. Our findings suggest that both FBC patients and sporadic TNBC patients should be tested for BRCA1/2 LGRs. Abstract : Large genomic rearrangements (LGRs) contribute to pathogenic mutations in BRCA1/2 . Here, we used multiplex ligation‐dependent probe amplification to identify BRCA1/2 LGRs in 1494 Chinese women with familial breast cancer or sporadic triple‐negative breast cancer who did not harbour BRCA1/2 small‐range mutations. We further identified the breakpoints of the BRCA1/2 LGRs, investigated the underlying mechanisms contributing to these mutations and explored the clinical relevance of BRCA1/2 LGRs.