RT Journal Article SR Electronic T1 The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer JF Cancer Biology and Medicine JO Cancer Biol Med FD China Anti-Cancer Association SP 1002 OP 1013 DO 10.20892/j.issn.2095-3941.2020.0089 VO 17 IS 4 A1 Fan, Yue A1 Ying, Haifeng A1 Wu, Xueying A1 Chen, Huan A1 Hu, Ying A1 Zhang, Henghui A1 Wu, Lijia A1 Yang, Ying A1 Mao, Beibei A1 Zheng, Lan YR 2020 UL http://www.cancerbiomed.org/content/17/4/1002.abstract AB Objective: Currently, there is an urgent need to identify immunotherapeutic biomarkers to increase the benefit of immune checkpoint inhibitors (ICIs) for patients with gastric cancer (GC). Homologous recombination deficiency (HRD) can modify the tumor immune microenvironment by increasing the presence of tumor-infiltrating lymphocytes and therefore might serve as a biomarker of immunotherapeutic response. We aimed to analyze the mutational pattern of HR-associated genes in Chinese patients with GC and its relevance to the tumor immune profile and clinical immunotherapeutic response.Methods: A panel of 543 cancer-associated genes was used to analyze genomic profiles in a cohort comprising 484 Chinese patients with GC. Correlations between HR gene mutations and tumor immunity or clinical outcomes were identified via bioinformatic analysis using 2 GC genomic datasets (TCGA and MSK-IMPACT).Results: Fifty-one of the 484 (10.54%) patients carried at least one somatic mutation in an HR gene; ATM (16/484, 3.31%) was among the most frequently mutated HR genes in the Chinese cohort. Mutations in HR genes were associated with elevated tumor mutational burden, enhanced immune activity, and microsatellite instability status. In the MSK-IMPACT cohort comprising 49 patients with stomach adenocarcinoma or gastroesophageal junction adenocarcinoma treated with ICIs, patients with HR-mut GC (n = 12) had significantly better overall survival than those with HR-wt GC (n = 37) (log-rank test, P < 0.05).Conclusions: Our data suggest that detection of somatic mutations in HR genes might aid in identifying patients who might benefit from immune checkpoint blockade therapy.