Abstract P4-11-02: Novel BRCA1 and BRCA2 genomic rearrangements in Southern Chinese breast/ovarian cancer patients

Abstract

Background and Aims: Germline mutations in the two breast cancer susceptibility genes, BRCA1 and BRCA2 account for a significant portion of hereditary breast/ovarian cancer. Most of the BRCA mutations reported in Southern Chinese patients were point mutations, small deletions, and insertions. The spectrum of large genomic rearrangement (LGR) is largely unknown. Here we perform the first study on the LGR of BRCA genes in a Hong Kong Chinese population. We aimed to determine the spectrum of BRCA LGRs in Southern Chinese patients with breast cancer. Methods: A total of 555 clinically high-risk breast and/or ovarian cancer patients were recruited from the Hong Kong Hereditary Breast Cancer Family Registry, diagnosed from March 2007 to November 2011. Multiplex ligation-dependent probe amplification (MLPA) for detecting BRCA LGRs together with comprehensive BRCA1 and BRCA2 gene sequencing of all coding exons were performed. cDNA sequencing of the LGRs was performed to locate the breakpoint of the deletions. Results: Overall BRCA1/2 mutation prevalence among this cohort was 12.4% (69/555). Among the 69 mutations identified, 4 novel LGRs (2 in BRCA1 and 2 in BRCA2) were detected only by MLPA but not full gene sequencing. Overall the LGR genes accounted for 5.8% (4/69) of all BRCA mutations in our cohort, 6.9% (2/29) of all BRCA1 mutations and 5% (2/40) of all BRCA2 mutations. Conclusions: These findings highlight the LGR spectrum of BRCA1 and BRCA2 genes in Southern Chinese breast cancer patients. LGR testing together with BRCA1/2 full gene sequencing is superior to other methods for comprehensive BRCA1/2 analysis in clinical settings. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-11-02.