Identifying molecular drivers of gastric cancer through next-generation sequencing

Abstract

Gastric cancer is the second most common cause of cancer-related death in the world, representing a major global health issue. The high mortality rate is largely due to the lack of effective medical treatment for advanced stages of this disease. Recently next-generation sequencing (NGS) technology has become a revolutionary tool for cancer research, and several NGS studies in gastric cancer have been published. Here we review the insights gained from these studies regarding how use NGS to elucidate the molecular basis of gastric cancer and identify potential therapeutic targets. We also discuss the challenges and future directions of such efforts.

Keywords: Gastric cancer; Gene fusion; Next-generation sequencing; RNA sequencing; Somatic mutation; Therapeutic target.

Fig.1. A comparison of most significantly mutated genes identified in the two whole-exome sequencing studies

Top significantly mutated genes (FDR < 0.2) were obtained from each study, respectively; and genes previously known to associate with gastric cancer are shown in bold.

Fig.2. Gene fusions discovered in gastric cancer by NGS studies

(A) A fusion between CDK12 exon 12 and ERBB2 intron 4 in MKN7 cells; (B) a fusion between NEUROD2 exon 1 and ERBB2 exon 8 in MKN17 cells; and (C) a fusion between AGTRAP exon 5 and BRAF exon 8 in a gastric tumor sample. (A) and (B) are reproduced with permission from Zang et al. [32], and (C) is reproduced from Palanisamy et al. [46]