Journal
JOURNAL OF PATHOLOGY
Volume 216, Issue 4, Pages 471-482Publisher
WILEY
DOI: 10.1002/path.2424
Keywords
gastric cancer; array CGH; expression profile; oligonucleotide microarray
Funding
- Ministry of Education, Science, Sports and Culture of Japan
- Grants-in-Aid for Young Scientists (B) [20790286]
- Grants-in-Aid for Scientific Research [20790286] Funding Source: KAKEN
Ask authors/readers for more resources
Genomic copy number aberrations (CNAs) are believed to play a major role in the development and progression of human cancers. Although many CNAs have been reported in gastric cancer, their genome-wide transcriptional consequences are poorly understood. In this study, to reveal the impact of CNAs on genome-wide expression in gastric cancer, we analysed 30 cases of gastric cancers for their CNAs by array comparative genomic hybridization (array CGH) and 24 of these 30 cases for their expression profiles by oligonucleotide-expression microarray. We found that with the application of laser microdissection, most CNAs were detected at higher frequency than in previous studies. Notably, gain at 20q13 was detected in almost all cases (97%), suggesting that this may play an important role in the pathogenesis of gastric cancer. By comparing the array CGH data with expression profiles of the same samples, we showed that both genomic amplification and deletion strongly influence the expression of genes in altered genomic regions. Furthermore, we identified 125 candidate genes, consisting of 114 up-regulated genes located in recurrent regions (>10%) of amplification and 11 down-regulated genes located in recurrent regions of deletion. Up-regulation of several candidate genes, such as CDC6, SEC61G, ANP32E, BYSL and FDFT1, was confirmed by immunohistochemistry. Interestingly, some candidate genes were localized at genomic loci adjacent to well-known genes such as EGFR, ERBB2 and SMAD4, and concordantly deregulated by genomic alterations. Based on these results, we propose that our list of candidate genes may contain novel genes involved in the pathogenesis of advanced gastric cancer. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available