Comprehensive characterization of the genomic alterations in human gastric cancer

Juan Cui, Yanbin Yin, Qin Ma, Guoqing Wang, Victor Olman, Yu Zhang, Wen Chi Chou, Celine S. Hong, Chi Zhang, Sha Cao, Xizeng Mao, Ying Li, Steve Qin, Shaying Zhao, Jing Jiang, Phil Hastings, Fan Li, Ying Xu

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)86-95
Number of pages10
JournalInternational Journal of Cancer
Volume137
Issue number1
DOIs
StatePublished - Jul 1 2015

Keywords

  • bioinformatics
  • cancer mutations
  • gastric cancer
  • genomic variations
  • next-generation sequencing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Cui, J., Yin, Y., Ma, Q., Wang, G., Olman, V., Zhang, Y., Chou, W. C., Hong, C. S., Zhang, C., Cao, S., Mao, X., Li, Y., Qin, S., Zhao, S., Jiang, J., Hastings, P., Li, F., & Xu, Y. (2015). Comprehensive characterization of the genomic alterations in human gastric cancer. International Journal of Cancer, 137(1), 86-95. https://doi.org/10.1002/ijc.29352