Abstract 1424P
Background
Although most gastric cancers (GC) are sporadic, but familial cases also occur in GC such as hereditary diffuse GC and familial intestinal GC. Most familial patients with GC are probably due to heritable pathogenic mutations. Among these familial GC, only hereditary diffuse GC is genetically explained which was known as to be caused by germline alterations of CDH1. Herein, we evaluated the genetic characteristic that mainly focused on germline mutation in Chinese patients with GC.
Methods
The Formalin-Fixed Paraffin-Embedded (FFPE) tissues from GC patients who have underwent next generation sequencing (NGS) from February, 2018 to December, 2020 in 3DMed Clinical Laboratory Inc. (a College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory) were analyzed. The single nucleotide variants (SNVs), germline mutation, copy number variants (CNVs) and gene rearrangements data of these patients were analyzed.
Results
NGS results revealed that there were 57.8% (1069/1850) patients carry germline mutation, 13.46% (248/1850) were germline deletion polymorphism of the gene Bcl-2 like protein 11 (BCL2L11, BIM), and except for benign, likely benign, and variant of unknown clinical significance, 2.8% (52/1850) patients were pathogenic mutation in germline. Among the pathogenic germline mutation, the top germline mutation genes were BRCA2 0.70% (13/1850), ATM 0.70% (13/1850), CHEK2 0.27% (5/1850), PALB2 0.27% (5/1850), CDH1 0.22% (4/1850), MUTYH 0.22% (4/1850), MSH1 0.11% (2/1850), MSH6 0.11% (2/1850), PMS2 0.11% (2/1850), BRCA1 0.11% (2/1850), TSC2 0.11% (2/1850).
Conclusions
Although the incidence of familial gastric cancer is low, the spectrum of germline mutations related to genetic risk is extensive. It is necessary to accurately manage the genetic risk of gastric cancer，consideration should be given to testing more than CDH1 in the germline mutation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.