Characteristics of germline DNA damage response gene mutations in ovarian cancer in Southwest China.

e17606 Background: DNA damage response (DDR) pathway is responsible for repairing endogenous or exogenous DNA damage to maintain the stability of the cell genome. Germline mutations of DDR genes are potentially predictive and prognostic biomarkers for oncotherapy and may predispose carries to some malignancies. We aimed to profile the characteristics of germline DDR gene mutations in ovarian cancer treated in our center to provide highlight on regional disparity and susceptibility genes. Methods: We retrospectively and unselectively enrolled a cohort of patients diagnosed as advanced epithelial ovarian cancer from October 2016 to October 2020, who had complete clinicopathological data and signed informed consent for gene testing. In total, peripheral blood samples from 432 patients were collected in our center and evaluated on specific germline alterations. This study was approved by the Medical Ethics Committee of West China Second University Hospital, Sichuan University (Ethical Lot Number 20200076). Results: The most observed mutated genes were FANCD2 (47%), BRCA1 (27%), BRCA2 (27%), ERCC5 (18%) and RECQL4 (17%). The frequency of missense mutation was higher than other mutation types in most genes, except FANCD2, TSC2 and PHOX2B. Deleterious DDR gene mutations and deleterious homologous recombination repair gene mutations were detected in 346 patients (80.1%) and 240 patients (55.6%), respectively. The most observed genes with deleterious mutation were BRCA1 (18.5%), BRCA2 (12.5%), ERCC5 (6%), MLH1 (5.8%), PALB2 (3.7%) and ERCC4 (3.7%). The prevalence of BRCA2 deleterious mutations is higher than other studies (patients mainly from Eastern China), and so are the mismatch repair genes. Furthermore, we pointed out that deleterious mutations of FNACD2 and RECQL4 are potential ovarian cancer susceptibility genes and may predispose carriers to ovarian cancer. Conclusions: Our study presented here showed the germline DDR gene mutation spectrum of ovarian cancer patients in Southwest China, which is different from other regions of China in some genes. And we found germline FANCD2 and RECQL4 deleterious mutations were likely ovarian cancer susceptibility sites, which should draw more attention in patient management and genetic counseling.