Whole Exome Sequencing Revealed Rare Variants in BRCA2, RAD51D, FANGC, CYP24A1 Genes in Breast/Ovarian Cancer...

Breast cancer is a public health problem with increasing incidence, prevalence, and mortality worldwide. Germline variants in the DNA repair genes BRCA1/2 are involved in the pathogenesis of hereditary breast/ovarian cancer. However, for many ethnic groups that are isolated geographically worldwide, founder variants of breast cancer still have not been found. In this study, we provide whole exome sequencing data performed in a group of breast/ovarian cancer patients who belong to the Buryats.

Our study included 56 Buryat patients with histologically confirmed primary breast/ovarian cancer who completed an anonymous questionnaire about basic information and nationality. Genomic DNA was isolated from peripheral blood leukocytes. Libraries were prepared using a BGI Optimal DNA Library Prep kit (MGI, China). An Agilent SureSelect Human All Exon V6 kit (Agilent, USA) was used for hybridization. High-throughput sequencing was performed on a DNA nanoball sequencing platform DNBSeq-G400 (MGI, China).  Result: In the overall group of patients with signs of hereditary breast/ovarian cancer, likely pathogenic/pathogenic variants were detected in 16% (9/56). We have discovered likely pathogenic/pathogenic variants that can either directly (BRCA2, RAD51D, FANCG) or indirectly (POLR2C, FOXL2, GDF9, CYP21A4) initiate breast/ovarian cancer. For the first time, three rare germinal variants in the BRCA2 gene were detected in a small Buryat ethnic group. Further studies are required to confirm their role in the pathogenesis of breast /ovarian cancer in this ethnic group. We found that the RAD51D gene variant c.757C>T is recurrent and was observed in 4% of Buryat patients with breast/ovarian cancer.

For the first time, rare germinal variants in the BRCA2, RAD51D, FANGC, CYP24A1 genes were detected in a small Buryat ethnic group. Our data are consistent with existing data showing that variants in the RAD51D gene may be involved in the pathogenesis of breast/ovarian cancer. We also showed that the Mongolic-speaking Buryat populations exhibited strong genetic resemblance to those of Chinese.