title: Integration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer.
abstract: BACKGROUND
  Genomic instability with frequent DNA copy number alterations is one of the key hallmarks of carcinogenesis. The chromosomal regions with frequent DNA copy number gain and loss in human gastric cancer are still poorly defined. It remains unknown how the DNA copy number variations contributes to the changes of gene expression profiles, especially on the global level.
  
  
  RESULTS
  We analyzed DNA copy number alterations in 64 human gastric cancer samples and 8 gastric cancer cell lines using bacterial artificial chromosome (BAC) arrays based comparative genomic hybridization (aCGH). Statistical analysis was applied to correlate previously published gene expression data obtained from cDNA microarrays with corresponding DNA copy number variation data to identify candidate oncogenes and tumor suppressor genes. We found that gastric cancer samples showed recurrent DNA copy number variations, including gains at 5p, 8q, 20p, 20q, and losses at 4q, 9p, 18q, 21q. The most frequent regions of amplification were 20q12 (7/72), 20q12-20q13.1 (12/72), 20q13.1-20q13.2 (11/72) and 20q13.2-20q13.3 (6/72). The most frequent deleted region was 9p21 (8/72). Correlating gene expression array data with aCGH identified 321 candidate oncogenes, which were overexpressed and showed frequent DNA copy number gains; and 12 candidate tumor suppressor genes which were down-regulated and showed frequent DNA copy number losses in human gastric cancers. Three networks of significantly expressed genes in gastric cancer samples were identified by ingenuity pathway analysis.
  
  
  CONCLUSIONS
  This study provides insight into DNA copy number variations and their contribution to altered gene expression profiles during human gastric cancer development. It provides novel candidate driver oncogenes or tumor suppressor genes for human gastric cancer, useful pathway maps for the future understanding of the molecular pathogenesis of this malignancy, and the construction of new therapeutic targets.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Biao
authors.initials: B
authors.lastname: Fan
authors.forename: Somkid
authors.initials: S
authors.lastname: Dachrut
authors.forename: Ho
authors.initials: H
authors.lastname: Coral
authors.forename: Siu Tsan
authors.initials: ST
authors.lastname: Yuen
authors.forename: Kent Man
authors.initials: KM
authors.lastname: Chu
authors.forename: Simon
authors.initials: S
authors.lastname: Law
authors.forename: Lianhai
authors.initials: L
authors.lastname: Zhang
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
authors.forename: Suet Yi
authors.initials: SY
authors.lastname: Leung
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D002875:Chromosomes; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D020869:Gene Expression Profiling; D006801:Humans; D009857:Oncogenes / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins