Gastric Cancer Genomics: Advances and Future Directions

Abstract

Advancement in the field of cancer genomics is revolutionizing the molecular characterization of a wide variety of different cancers. Recent application of large-scale, next-generation sequencing technology to gastric cancer, which remains a major source of morbidity and mortality throughout the world, has helped better define the complex genomic landscape of this cancer. These studies also have led to the development of novel genomically based molecular classification systems for gastric cancer, reinforced the importance of classic driver mutations in gastric cancer pathogenesis, and led to the discovery of new driver gene mutations that previously were not known to be associated with gastric cancer. This wealth of genomic data has significant potential to impact the future management of this disease, and the challenge remains to effectively translate this genomic data into better treatment paradigms for gastric cancer.

Keywords: ACRG, Asian Cancer Research Group; CIN, chromosomal instability; Driver Gene Mutations; EBV, Epstein–Barr virus; EMT, epithelial-to-mesenchymal transition; GS, genomic stability; Gastric Cancer; Genomics; MSI, microsatellite instability; MSS, microsatellite stable; NGS, next-generation sequencing; Next-Generation Sequencing; PD-L, programmed death-ligand; RTK, receptor tyrosine kinase; TCGA, The Cancer Genome Atlas.

Figure 1

Molecular classifications of gastric cancers. TCGA molecular subtypes including EBV positive, MSI, GS, and CIN. ACRG molecular subtypes including MSI and MSS tumors with either MSS/EMT, TP53 activity (MSS/TP53⁺), or TP53 inactivity (MSS/TP53^-). Percentages represent the fraction of molecularly characterized gastric cancer samples belonging to each subtype.

Figure 2

Commonly mutated pathways in gastric cancers. NGS genomic studies have identified multiple pathways that contain genes that are mutated frequently in gastric cancers.