胃底腺型胃肿瘤11例分子遗传学特征分析

Gastric neoplasm of fundic-gland type:a molecular study of eleven cases

目的探讨胃底腺型胃肿瘤的分子特征及其发生、发展的机制。方法收集11例胃底腺型胃肿瘤标本,包括1例泌酸腺腺瘤和10例胃底腺型腺癌。原位杂交检测EB病毒核酸EBER,二代测序分析GNAS、KRAS、NRAS、BRAF、PIK3CA、TP53、APC、CTNNB1、HER-2、MLH1、MSH2、MSH6、PMS2等基因的变异信息,并复习相关文献。结果11例胃底腺型腺癌中检出6例GNAS、2例KRAS及1例TP53错义突变,其中2例同时发生GNAS、KRAS错义突变;泌酸腺腺瘤未检出GNAS、KRAS突变。11例胃底腺型胃肿瘤均未检出APC、CTNNB1、NRAS、BRAF、PIK3CA、HER-2、MLH1、MSH2、MSH6、PMS2基因非同义突变,未检出EB病毒。结论胃底腺型腺癌具有分子异质性,GNAS突变较KRAS、TP53突变常见,尚未发现EB病毒相关及微卫星不稳定。

Purpose To analyze the molecular features of gastric neoplasm of fundic-gland type(GNFG)and to explore the possible mechanism of tumor development.Methods Eleven cases of GNFG were collected from Peking University International Hospital and Liaocheng People’s Hospital,including 1 oxyntic gland adenoma(OGA)and 10 gastric adenocarcinomas of fundic-gland type(GAFG).The nucleic acid of EBER was detected by in situ hybridization and the next generation sequencing was used to analyze the mutation of GNAS,KRAS,NRAS,BRAF,PIK3CA,TP53,APC,CTNNB1,HER-2,MLH1,MSH2,MSH6,PMS3 and other genes.The related literatures were reviewed.Results Missense mutations including 6 cases of GNAS,2 cases of KRAS and 1 case of TP53 were detected in GAFG,of which 2 cases had GNAS and KRAS missense mutations at the same time.However,GNAS and KRAS mutations were not founded in OGA.No nonsynonymous mutation happened in APC,CTNNB1,NRAS,BRAF,PIK3CA,HER-2,MLH1,MSH2,MSH6 and PMS2 genes of all the cases.Also EBER was totally negative.Conclusion GAFG has molecular heterogeneity,of which GNAS mutation is relatively more common than KRAS and TP53 mutations.Up to now,there are no EBV-related cases and no microsatellite instability in GNFG.