Although histological and molecular (genomic and transcriptomic) classifications have been well studied for gastric cancer (GC), targeted therapies for GC are still limited. E-cadherin (encoded by CDH1) is a member of the cadherin family of calcium dependent cell adhesion molecules and plays a major role in the process of intercellular adhesion between epithelial cells. Frequent CDH1 mutations are characteristics of genomically stable gastric tumors and are associated with poor prognosis, but lack effective therapies. Most of the earlier works on CDH1 mutation of GC had been on familial cases and focused on the germline mutation, which is a known risk factor for hereditary DGC. Lack of sufficient studies explored the molecular features of CDH1-mutated (MT) GC, and identified potential druggable targets for these cohort. Herein we aim to understand the specific mutation profile and enriched pathways in CDH1-MT GC, which could help to discover novel drug targets.
This is the largest study to investigate the distinct genomic landscape between CDH1-MT and WT GC. Our data indicate GC patients with CDH1 mutation could potentially benefit from agents targeting DNA repair pathway, while immunotherapy may be of lower efficacy in this cohort based on lower CPS score. Efficiency of these therapeutic targets and enriched pathways in CDH1- Mut GC warrant further investigation.Download Publication