• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Oncotarget >The chronological sequence of somatic mutations in early gastric carcinogenesis inferred from multiregion sequencing of gastric adenomas
【2h】

The chronological sequence of somatic mutations in early gastric carcinogenesis inferred from multiregion sequencing of gastric adenomas

机译：从胃腺瘤多区测序推论早期胃癌发生过程中体细胞突变的时间顺序。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Mutation profiles and intratumoral heterogeneity are not well understood for benign gastric adenomas, some of which progress into malignant gastric adenocarcinomas. In this study, we performed whole-exome sequencing of three microsatellite stable (MSS) and two microsatellite instability-high (MSI-H) gastric adenomas with three regional tumor biopsies per case. We observed that the mutation abundance of benign gastric adenomas was comparable to those of gastric adenocarcinomas, suggesting that the mutational makeup for gastric carcinogenesis may already be achieved in benign adenomas. The extent of intratumoral heterogeneity was more substantial for MSS genomes in that only 1% - 14% of somatic mutations were common across the regional biopsies or ‘public’, while 50% - 94% of mutations were public in MSI-H gastric adenomas. We observed biallelic, loss-of-functional events of APC with truncating mutations and/or 5q losses for all cases, mostly as public events. All MSS gastric adenomas also harbored ARID2 truncating mutations, often as multiple, region-specific ones indicative of convergent evolution. Hotspot missense mutations on known cancer genes such as ERBB2 and KRAS were largely observed as region-specific aberrations. These findings suggest that biallelic functional APC inactivation initiates the gastric carcinogenesis and is followed by mutations of histone modifiers and then activation of known cancer-related genes. As the first exome-wide multi-region mutational profiling of gastric adenomas, our study provides clues on the chronological sequence of somatic mutations and their clonal architectures in early gastric carcinogenesis.
机译：良性胃腺瘤的突变特征和肿瘤内异质性尚不十分清楚，其中一些进展为恶性胃腺癌。在这项研究中，我们对每个病例​​进行了三个微卫星稳定（MSS）和两个微卫星不稳定性高（MSI-H）胃腺瘤的全外显子测序，每个病例进行了三个区域活检。我们观察到，良性胃腺瘤的突变丰度与胃腺癌的突变丰度相当，这表明在良性腺瘤中可能已经实现了针对胃癌发生的突变构成。对于MSS基因组而言，肿瘤内异质性的程度更大，因为只有1％-14％的体细胞突变在区域活检或“公共”中是常见的，而50％-94％的突变在MSI-H胃腺瘤中是公共的。我们观察到在所有情况下，APC的双等位基因功能丧失事件均具有截短突变和/或5q丧失，主要是作为公共事件。所有MSS胃腺瘤也都带有ARID2截短突变，通常为多个区域特异性突变，表明会聚进化。众所周知，ERBB2和KRAS等已知癌症基因上的热点错义突变是区域特异的畸变。这些发现表明，双等位基因功能性APC失活启动了胃癌的发生，随后是组蛋白修饰剂的突变，然后激活了已知的癌症相关基因。作为胃腺瘤的第一个全基因组范围的多区域突变谱，我们的研究为早期胃癌发生过程中体细胞突变的时间序列及其克隆结构提供了线索。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号