Associations Between Molecular Characteristics of Late-Stage Gastric Cancer in Patients of Western and Asian Origin

A study led by Yelena Janjigian, MD, has analyzed the landscape of late-stage gastric cancer (GC) using data from the KEYNOTE-059, -061, and -062 studies in patients of Western and Asian origin.

Data was compared with early-stage GC data from The Cancer Genome Atlas (TCGA). Bulk DNA taken from pretreatment tumor samples was analyzed using whole-exome sequencing (WES; KEYNOTE-059, KEYNOTE-061) and FoundationOneCDx (KEYNOTE-062) to determine TCGA-defined molecular subtypes (Epstein-Barr virus-positive, microsatellite instability-high [MSI-H], genomically stable [GS], or chromosomal instability [CIN]), genomic alterations, homologous recombination deficiency (HRD), and tumor mutational burden (TMB). RNA sequencing was used to analyze gene expression signatures.

When comparing combined WES and FoundationOneCDx data from each KEYNOTE trial with data from TCGA, the MSI-H subtype was found to be lower in patients of Western (5% vs 22%) and Asian origin (5% vs 19%). Meanwhile, a comparison of WES data from KEYNOTE-059 and -061 with the TCGA dataset showed that the occurrence of the GS subtype was higher (36% vs 21%) in patients of Western or Asian origin.

Of subtypes in KEYNOTE-059 and -061, HRD scores and TMB were highest in CIN and MSI-H subtypes, respectively. The most common genomic characteristic based on the combined analysis of all three trials was the TP53 mutation. Gene expression signature distributions were similar between patients.