Gastric cancer (GC) is one of the leading cause of cancer death in China, which is mainly caused by environmental and genetic risk factors. By far, the nature of the genetic factors related to gastric cancer has not been well-studied. The aim of this study was to assess the frequency of germline mutations in Chinese gastric cancer population.
Genomic profiling of DNA was performed through next-generation sequencing (NGS) on tissue or liquid biopsy from patients with gastric cancer between January 01, 2017 and May 07, 2019. Patients with germline pathogenic mutations were identified, and their clinical information were collected.
750 gastric cancer patients were ultimately included for analysis. There were 476 (63.5%) male and 274 (36.5%) female patients. The median age was 61 (range, 26-88). A total of 27 (3.6%) pathogenic germline pathogenic mutations were identified in 13 genes from these patients. The mutations fell most frequently in BRCA2 (0.93%), ATM (0.67%), PALB2 (0.4%), CHEK2 (0.27%), and CDH1 (0.27%), which has been previously reported to underlie hereditary diffuse gastric cancer. Of all these mutations, 9 (69.2%) genes lay in the DNA damage repair pathways, including BRCA1, BRCA2, ATM, PALB2, CHEK2, MRE11A, ATR, and two DNA mismatch repair genes, MLH1 and MSH6, the mutation of which usually result in the presence of microsatellite instability (MSI) in tumor tissues.
This is the first study to explore the spectrum of pathogenic germline mutations in Chinese patients with gastric cancer. Our study has provided valuable clues for the assessment of the corresponding genetic susceptibility in gastric cancer.
Clinical trial identification
Legal entity responsible for the study
Beijing Cancer Hospital.
Has not received any funding.
Z. Zhao: Full / Part-time employment: 3D Medicines Inc. Y. Zhang: Full / Part-time employment: 3D Medicines Inc. S. Cai: Full / Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.