Genome-wide analysis of DNA copy number alterations and gene expression in gastric cancer

被引：101

作者：

Tsukamoto, Y. ^{[1
]}

Uchida, T. ^{[1
,2
]}

Kaman, S. ^{[3
]}

Noguchi, T. ^{[4
]}

Nguyen, L. T. ^{[1
,5
]}

Tanigawa, M. ^{[6
]}

Takeuchi, I. ^{[7
]}

Matsuura, K. ^{[1
]}

Hijiya, N. ^{[1
]}

Nakada, C. ^{[1
]}

Kishida, T. ^{[2
]}

Kawahara, K. ^{[8
]}

Ito, H. ^{[9
]}

Murakami, K. ^{[5
]}

Fujioka, T. ^{[5
]}

Seto, M. ^{[3
]}

Moriyama, M. ^{[1
]}

机构：

[1] Oita Univ, Fac Med, Dept Mol Pathol, Yufu City, Oita 5795593, Japan

[2] Oita Univ, Fac Med, Dept Human Environm & Social Med, Yufu City, Oita 5795593, Japan

[3] Aichi Canc Ctr, Div Mol Med, Nagoya, Aichi 464, Japan

[4] Oita Univ, Fac Med, Dept Gastrointestinal, Yufu City, Oita 5795593, Japan

[5] Oita Univ, Fac Med, Dept Gastroenterol, Yufu City, Oita 5795593, Japan

[6] Oita Univ, Div Biomol Med & Med Imaging, Yufu City, Oita 5795593, Japan

[7] Nagoya Inst Technol, Dept Comp Sci Sci & Engn Simulat, Nagoya, Aichi, Japan

[8] Oita Univ, Fac Med, Dept Surg 2, Yufu City, Oita 5795593, Japan

[9] Tottori Univ, Fac Med, Div Organ Pathol, Dept Pathol & Microbiol, Yonago, Tottori 683, Japan

来源：

JOURNAL OF PATHOLOGY | 2008年 / 216卷 / 04期

关键词：

gastric cancer; array CGH; expression profile; oligonucleotide microarray;

D O I：

10.1002/path.2424

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：471 / 482

页数：12

共 26 条

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