Comprehensive characterization of the genomic alterations in human gastric cancer

被引：64

作者：

Cui, Juan ^{[1
,2
]}

Yin, Yanbin ^{[2
]}

Ma, Qin ^{[2
]}

Wang, Guoqing ^{[3
]}

Olman, Victor ^{[2
]}

Zhang, Yu ^{[4
]}

Chou, Wen-Chi ^{[2
]}

Hong, Celine S. ^{[2
]}

Zhang, Chi ^{[2
]}

Cao, Sha ^{[2
]}

Mao, Xizeng ^{[2
]}

Li, Ying ^{[4
]}

Qin, Steve ^{[5
]}

Zhao, Shaying ^{[2
]}

Jiang, Jing ^{[3
]}

Hastings, Phil ^{[6
]}

Li, Fan ^{[3
]}

Xu, Ying ^{[2
,4
]}

机构：

[1] Univ Nebraska, Dept Comp Sci & Engn, Lincoln, NE 68588 USA

[2] Univ Georgia, Inst Bioinformat, Dept Biochem & Mol Biol, Computat Syst Biol Lab, Athens, GA 30602 USA

[3] Jilin Univ, Coll Bethune Sch Med, Changchun, Peoples R China

[4] Jilin Univ, Coll Comp Sci & Technol, Changchun, Peoples R China

[5] Emory Univ, Biostat & Bioinformat Dept, Atlanta, GA 30322 USA

[6] Baylor Coll Med, Dept Mol & Human Genet, Housston, TX USA

来源：

INTERNATIONAL JOURNAL OF CANCER | 2015年 / 137卷 / 01期

关键词：

gastric cancer; next-generation sequencing; bioinformatics; genomic variations; cancer mutations; SOMATIC MUTATIONS; FRAGILE SITES; DNA-DAMAGE; PATTERNS; CELLS; IDENTIFICATION; REARRANGEMENT; ASSOCIATION; ACTIVATION; SIGNATURES;

D O I：

10.1002/ijc.29352

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Gastric cancer is one of the most prevalent and aggressive cancers worldwide, and its molecular mechanism remains largely elusive. Here we report the genomic landscape in primary gastric adenocarcinoma of human, based on the complete genome sequences of five pairs of cancer and matching normal samples. In total, 103,464 somatic point mutations, including 407 nonsynonymous ones, were identified and the most recurrent mutations were harbored by Mucins (MUC3A and MUC12) and transcription factors (ZNF717, ZNF595 and TP53). 679 genomic rearrangements were detected, which affect 355 protein-coding genes; and 76 genes show copy number changes. Through mapping the boundaries of the rearranged regions to the folded three-dimensional structure of human chromosomes, we determined that 79.6% of the chromosomal rearrangements happen among DNA fragments in close spatial proximity, especially when two endpoints stay in a similar replication phase. We demonstrated evidences that microhomology-mediated break-induced replication was utilized as a mechanism in inducing approximate to 40.9% of the identified genomic changes in gastric tumor. Our data analyses revealed potential integrations of Helicobacter pylori DNA into the gastric cancer genomes. Overall a large set of novel genomic variations were detected in these gastric cancer genomes, which may be essential to the study of the genetic basis and molecular mechanism of the gastric tumorigenesis.

引用

页码：86 / 95

页数：10

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