Comprehensive molecular characterisation of gastric adenocarcinoma (The Cancer Genome Atlas)
Sequencing 295 stomach cancers divided them into four molecular groups, Epstein-Barr virus-positive, microsatellite unstable, genomically stable and chromosomally unstable, each with distinct drivers and potential therapies.
Overview
Integrated genomic analysis by The Cancer Genome Atlas of 295 primary gastric adenocarcinomas identifying four subtypes: Epstein-Barr virus-positive (PIK3CA mutations, PD-L1/2 amplification), microsatellite unstable (hypermutation), genomically stable (diffuse histology, RHOA and CLDN18-ARHGAP fusions) and chromosomal instability (TP53 mutation, receptor tyrosine kinase amplifications).
- Four molecular subtypes with distinct genomic features.
- Microsatellite-unstable tumours in about 22 percent and Epstein-Barr virus-positive in about 9 percent of the cohort.
The immunotherapy sensitivity of microsatellite-unstable and Epstein-Barr virus-positive gastric cancer and the claudin 18.2 and HER2 targets map onto these subtypes.
- Subtypes are not yet used directly to choose treatment beyond microsatellite status and HER2.