Pathogenic Germline Mutations in Chinese Patients with Gastric Cancer Identified by Next-Generation Sequencing

Gastric cancer (GC) is one of the leading causes of cancer death in China, while the nature of genetic factors related to GC has not been well-studied.

To assess the inherited genetic factors regarding pathogenic germline mutations in Chinese GC population.

Genomic profiling of DNA was performed through next-generation sequencing with 381 cancer-related genes on tissue from patients with GC between January 1, 2017, and May 7, 2019.

470 GC patients were included for analysis. A total of 28 (6.0%) patients were identified to harbor 25 different pathogenic or very likely pathogenic germline mutations in 15 genes. The variants fell most frequently in BRCA2 (n = 6, 1.28%), CHEK2 (n = 5, 1.06%), MUTYH (n = 3, 0.64%), CDH1 (n = 2, 0.43%), and ATM (n = 2, 0.43%). Of all the germline-mutated genes, 66.7% (n = 10) lay in the DNA damage repair pathways. Seven patients were identified to have a high TMB status, among whom two were also identified as MSI-H. Overall, 20 out of the 28 patients (71.4%) carried clinically actionable mutations.

Our study has depicted the spectrum of pathogenic germline mutations in Chinese GC patients, which may provide valuable clues for the assessment of the genetic susceptibility and clinical management in GC.