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

Abstract

Background: 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. Objectives: To assess the inherited genetic factors regarding pathogenic germline mutations in Chinese GC population. Methods: 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. Results: 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. Conclusions: 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.

Somatic NGS Analysis of DNA Damage Response (DDR) Genes ATM, MRE11A, RAD50, NBN, and ATR in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemo-Radiotherapy

“…The incidence of RAD50 mutations in our series is in agreement with TCGA data and previous reports. Zhou et al [ 26 ] reported 3% of RAD50 non-silent mutations in a large series of 406 Chinese samples of CRC; however, the fraction of rectal cancer was not specified and the relationship with radiotherapy treatment was not investigated [ 27 ].…”

Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers

“…In his family, nine relatives deceased for gastric cancer. Although not frequently, pathogenic variants in ATM have been previously described in patients with GC [ 80 , 81 , 82 ]. PC remains one of the most lethal solid malignancies.…”

DNA Damage Repair and Current Therapeutic Approaches in Gastric Cancer: A Comprehensive Review

“…Gastric cancer is the fourth and seventh leading cause of new cancer cases in males and females, respectively, and the fourth and fifth leading cause of cancerrelated death in males and females, respectively (Hyuna et al, 2021). Most new cases occur in developing countries, especially in China (Zhou et al, 2020). The global incidence of gastric cancer is 42.6% and the mortality rate is 45.0% (Ferlay et al, 2014).…”