The mutation landscape of multiple cancer predisposition genes in Chinese familial/hereditary breast cancer families.

OBJECTIVE

Approximately 5%-10% of breast cancer (BC) patients display familial traits that are genetically inherited among the members of a family. The purpose of this study was to profile the germline mutations in 43 genes with different penetration rates and their correlations with phenotypic traits in Chinese familial BC families.

METHODS

Ion Torrent S5™-based next generation sequencing was conducted on 116 subjects from 27 Chinese familial BC families.

RESULTS

Eighty-one germline mutations in 27 BC predisposition genes were identified in 82.8% (96/116) of the cases. Among these, 80.8% of the mutated genes were related to DNA damage repair. Fourteen possible disease-causing variants were identified in 13 of 27 BC families. Only 25.9% (7/27) of the BC families exhibited hereditary deficiency in genes, while 22.2% of the BC families exhibited defects in genes. In all, 41.7% (40/96) of the mutation carriers had mutations, 88.5% (85/96) had mutations, and 30.2% (29/96) had both and mutations. The BC patients with mutations had a higher risk of axillary lymph node metastases than those without mutations ( < 0.05). However, the BC patients with mutations frequently had a higher occurrence of benign breast diseases than those without mutations ( < 0.05).

CONCLUSIONS

In addition to , genetic variants in DNA repair genes might play significant roles in the development of familial/hereditary BC. Therefore, profiling of multiple BC predisposition genes should be more valuable for screening potential pathogenic germline mutations in Chinese familial/hereditary BC.