Genetic features of multicentric/multifocal intramucosal gastric carcinoma
Genetic features of multicentric/multifocal intramucosal gastric carcinoma
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DOI：
10.1002/ijc.31578
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发表时间：
2018-10-15
影响因子：
6.4
通讯作者：
Marusawa, Hiroyuki
中科院分区：
文献类型：
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作者：
Mizuguchi, Aya;Takai, Atsushi;Marusawa, Hiroyuki
幽门螺杆菌（Helicobacter pylori，H. pylori）感染可导致胃癌的发生。多发性胃癌可以同时和/或异时发生，这一发现提示慢性炎症H。幽门感染的胃粘膜。然而，炎症胃中多发性肿瘤发生的遗传基础尚不清楚。在这项研究中，我们分析了41例同时或异时发生于19例H.幽门感染在41例粘膜内胃癌中，9例（22%）表现为MSI，其余32例（78%）表现为微卫星稳定（MSS）表型。异时性多发性粘膜内胃癌通过个体获得遗传畸变表现出肿瘤间异质性。所有同步多发性粘膜内胃癌对共享一个共同的MSI/MSS配置文件，和CNA分析显示，同步多发性粘膜内胃癌对MSS表型共享共同的畸变的代表性肿瘤抑制基因，包括APC，TP 53，CDKN 2A，CDKN 2B的局灶性缺失。多区域CNA分析显示，异质性基因扩增/缺失，包括PDL 1扩增，在个体粘膜内胃癌亚群中存在共享主干遗传改变的情况下进化。这些数据表明，多发性胃癌的发展在一个多中心/多灶性的方式表现出的特点之间和肿瘤内异质性H。幽门感染的胃粘膜，而同时多发性粘膜内胃癌可能共享部分共同的遗传改变，可能通过共同的致癌途径。
Chronic gastritis caused by Helicobacter pylori (H. pylori) infection could lead to the development of gastric cancer. The finding that multiple gastric cancers can develop synchronously and/or metachronously suggests the development of field cancerization in chronically inflamed, H. pylori-infected gastric mucosa. The genetic basis of multiple tumorigenesis in the inflamed stomach, however, is not well understood. In this study, we analyzed the microsatellite instability (MSI) status and copy number aberrations (CNAs) of 41 multiple intramucosal early gastric cancers that synchronously or metachronously developed in 19 patients with H. pylori infection. Among the 41 intramucosal gastric carcinomas, 9 (22%) exhibited MSI, and the remaining 32 (78%) exhibited the microsatellite stable (MSS) phenotype. Metachronous multiple intramucosal gastric carcinoma exhibit inter-tumor heterogeneity by individually acquiring genetic aberrations. All synchronous multiple intramucosal gastric carcinoma pairs shared a common MSI/MSS profile, and CNA analysis revealed that synchronous multiple intramucosal gastric carcinoma pairs with the MSS phenotype shared common aberrations of representative tumor-suppressor genes, including focal deletion of APC, TP53, CDKN2A, and CDKN2B. Multiregional CNA analysis revealed that heterogeneous gene amplifications/deletions, including PDL1 amplification, evolved under the presence of shared trunk genetic alterations in a subpopulation of individual intramucosal gastric carcinomas. These data suggest that multiple gastric carcinomas develop in a multicentric/multifocal manner exhibiting features of inter- and intra-tumor heterogeneity in H. pylori-infected gastric mucosa, whereas synchronous multiple intramucosal gastric carcinomas could share partially common genetic alterations, possibly via common oncogenic pathways.