BACKGROUND

Hereditary factors contributed to breast cancer susceptibility. Low mutation prevalence was demonstrated in previous mutation screening in Chinese breast cancer patients. Multiple-gene sequencing may assist in discovering detrimental germline mutation in.

BRCA

negative breast cancers.

METHODS

A total of 384 Chinese subjects with any two of high-risk factors were recruited and screened by next-generation sequencing (NGS) for 30 cancer susceptible genes. Variants with a truncating, initiation codon or splice donor/acceptor effect, or with pathogenicity demonstrated in published literature were classified into pathogenic/likely-pathogenic mutations.

RESULTS

In total, we acquired 39 (10.2%) patients with pathogenic/likely-pathogenic germline mutations, including one carrying two distinct mutations. Major mutant non- genes were (n=11, 2.9%), (n=7, 1.8%), (n=6, 1.6%) and (n=5, 1.3%). Other mutant genes included (n=3, 0.8%), (n=2, 0.5%), (n=1, 0.3%), (n=1, 0.3%), (n=1, 0.3%), (n=1, 0.3%), (n=1, 0.3%) and (n=1, 0.3%). A splicing germline mutation, c.934-2A>G, was a hotspot (9/384, 2.3%) in Chinese breast cancer.

CONCLUSIONS

Among -negative breast cancer patients with high hereditary risk in China, 10.2% carried mutations in cancer associated susceptibility genes. and had relatively high mutation rates (2.9% and 1.8%). Multigene testing contributes to understand genetic background of -negative breast cancer patients with high hereditary risk.