关键词: 靶向捕获高通量测序技术, 早期乳腺癌胚系突变, 新发基因突变, 临床应用

Abstract:

Objective To explore germline mutations of early-stage breast cancer patients by next-generation sequencing and its correlation with clinicopathological features. Methods Ninety-nine female patients with early-stage breast cancer were selected and 21 breast cancer susceptible genes were sequenced by next-generation sequencing technology. The detected mutation sites were screened and classified,and statistical analysis was performed with clinical pathological characteristics. Results A total of 55 mutation sites in 18 genes were detected in 48 patients,including 45 missense mutations,1 nonsense mutation,8 indel mutations,and 1 splice mutation. The most mutated was the BRCA gene,and 10 mutation sites were detected. Of the 55 mutations,9（16.4%）were pathogenic mutations,4（7.3%）were harmless mutations,and 42（76.3%） were unknown mutations. The 15 newly discovered mutation sites in this study were not mentioned in the ExAC,ClinVar,dbSNP,and HGMD databases. Pathogenic germline mutations were statistically significant in different age groups（P=0.044）and different Ki67 statuses（P=0.024）. Pathogenic mutations were more likely to occur in patients aged more than 40 years and in Ki67-positive patients. Conclusions The next-generation sequencing is of great significance for screening breast cancer susceptible genes,which lays certain theoretical and experimental basis for individualized treatment.

Key words: Next-generation sequencing, Germline mutation,early-stage breast cancer, New gene mutation, Clinical application