Gene mutations in gastric cancer: a review of recent next-generation sequencing studies

Y. Lin, Z. Wu, W. Guo, J. Li

Gastric cancer (GC) is one of the most common malignancies worldwide. Although some driver genes have been identified in GC, the molecular compositions of GC have not been fully understood. The development of next-generation sequencing (NGS) provides a high-throughput and systematic method to identify all genetic alterations in the cancer genome, especially in the field of mutation detection. NGS studies in GC have discovered some novel driver mutations. In this review, we focused on novel gene mutations discovered by NGS studies, along with some well-known driver genes in GC. We organized mutated genes from the perspective of related biological pathways. Mutations in genes relating to genome integrity (TP53, BRCA2), chromatin remodeling (ARID1A), cell adhesion (CDH1, FAT4, CTNNA1), cytoskeleton and cell motility (RHOA), Wnt pathway (CTNNB1, APC, RNF43), and RTK pathway (RTKs, RAS family, MAPK pathway, PIK pathway) are discussed. Efforts to establish a molecular classification based on NGS data which is valuable for future targeted therapy for GC are introduced. Comprehensive dissection of the molecular profile of GC cannot only unveil the molecular basis for GC but also identify genes of clinical utility, especially potential and specific therapeutic targets for GC.