title: Comprehensive characterization of the genomic alterations in human gastric cancer.
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.
authors.affiliation: Department of Computer Science and Engineering, University of Nebraska-Lincoln, Lincoln, NE; Department of Biochemistry and Molecular Biology, Computational Systems Biology Laboratory, Institute of Bioinformatics, University of Georgia, Athens, GA.
authors.forename: Juan
authors.initials: J
authors.lastname: Cui
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Yin
authors.forename: Qin
authors.initials: Q
authors.lastname: Ma
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wang
authors.forename: Victor
authors.initials: V
authors.lastname: Olman
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Chou
authors.forename: Celine S
authors.initials: CS
authors.lastname: Hong
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Sha
authors.initials: S
authors.lastname: Cao
authors.forename: Xizeng
authors.initials: X
authors.lastname: Mao
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Steve
authors.initials: S
authors.lastname: Qin
authors.forename: Shaying
authors.initials: S
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Phil
authors.initials: P
authors.lastname: Hastings
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000821:virology; D000368:Aged; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D004279:DNA, Viral / Q000032:analysis; D014644:Genetic Variation; D015894:Genome, Human; D016481:Helicobacter Infections / Q000235:genetics*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D004279:DNA, Viral
keywords: bioinformatics; cancer mutations; gastric cancer; genomic variations; next-generation sequencing