HUANG Fei, CHEN Xin-ning, YU Li, JIANG Hui-qin, SHI Ting-yan, SHEN Min-na, ZHANG Chun-yan, PAN Bai-shen, WANG Bei-li, GUO Wei
Objective To investigate profiles of germline BRCA 1/2 mutations (gBRCAm) in patients with breast cancer，and its relationship between gBRCAm with clinicopathological characteristics. Methods A total of 146 patients with breast cancer in Zhongshan Hospital from Jun 2019 to Apr 2021 were enrolled in this study. gBRCAm were analyzed using next-generation sequencing. The clinicopathological data from 94 patients with breast cancer were available and reviewed， including age of onset， histological grade， lymph node status and expression of estrogen receptor (ER)，progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2). The relationship between gBRCAm and clinicopathological characteristics was analyzed by Chi-square and Fisher's exact test. Results The prevalence of gBRCAm in patients with breast cancer was 12.3%. The detection rate of gBRCAm was significantly higher than that in public database (P=0.023). 94.4% of the mutations occurred in the exons of BRCA 1/2， and 5.6% occurred in the splicing regions of the introns. Frameshift mutations， nonsense mutations， large fragment rearrangements， splicing sites and synonymous mutations account for 61.1%， 16.7%， 11.1%， 5.5% and 5.5%，respectively. Among them， 1 case has not been reported previously in public databases. Clinical characteristics such as age of onset (P<0.001)， familial cancer history (P=0.008)， bilateral breast cancer (P=0.001) and triple-negative breast cancer (P=0.025) were closely related to gBRCAm status. A higher frequency for BRCA 2 mutations was observed in ER and PR positive patients (P=0.041 and P=0.026). Conclusion Frameshift mutations account for the highest proportion， which locate in important functional gene domains. gBRCAm can be commonly detected in patients with early-onset， family history or triple-negative breast cancer.
