Exome Sequencing Identifies Early Gastric Carcinoma as an Early Stage of Advanced Gastric Cancer

Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC), whereas the prognosis of patients with advanced gastric cancer (AGC) remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes) and AGCs (3104 genes). A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010). The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.

胃癌是全球范围内癌症相关死亡的主要病因之一。早期胃癌（early gastric cancer, EGC）患者通过早期诊断与治疗可获得极佳预后，而进展期胃癌（advanced gastric cancer, AGC）患者的预后仍不容乐观。目前学界尚不清楚早期胃癌与进展期胃癌是两种独立的疾病实体，还是早期胃癌为进展期胃癌的始发阶段。本研究对4例早期胃癌患者的样本实施全外显子组测序（whole exome sequencing），并将测序结果与进展期胃癌样本的测序结果进行对比分析。在早期胃癌与进展期胃癌样本中，共计268个基因存在共同突变；此外，早期胃癌组额外检出516个独有的突变基因，进展期胃癌组则检出3104个独有的突变基因。与弥漫型胃癌相比，肠型胃癌中C>G碱基转换的发生频率显著更高（P=0.010）。DYRK3、GPR116、MCM10、PCDH17、PCDHB1、RDH5及UNC5C基因在早期胃癌中频繁发生突变，可能参与早期癌变进程。