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

Abstract

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.

Krüppel‐like factor 12 plays a significant role in poorly differentiated gastric cancer progression

“…Of multiple locus of gene amplification and deletion, amplification of 2p24, 3q26, 5p13, 5p15, 6p21, 7q21, 8p23, 8q22, 8q24, 10q26, 11p11, 11p13, 11q13, 16p13, 17q12, 19q12-13, 20q13 and loss of 4q34, 9p21, 10q23, 19p13, 19q13 were consistent with the previous report in gastric cancer tissue or gastric cancer cell lines. [10][11][12][13][14][15][16][17][18][19][20][21] Most amplification loci were unique to single patients. The results thus suggest genetic alternations are less frequent in poorly differentiated gastric cancers and vary among individuals.…”

Genetic Instability in Gastric Cancer

“…Tsukamoto et al observed higher frequencies of DNA copy number aberrations, especially in the case of 20q13 chromosome gain, which was detected in 97% of cases, compared to other studies (Tsukamoto et al, 2008). They used laser microdissection method to isolate tumour cells, therefore their samples contained fewer cells from tumour microenvironment.…”

A New Paradigm in the Treatment of Gastric Cancer

“…CIN is due to the imbalanced division of chromosomes to daughter cells upon mitosis and results in the loss or gain of DNA during cell division [14]. Copy number gains at 8q, 12q, 13q, 17q, and 20q and copy number losses at 3p, 4q, 5q, 15q, 16q, and 17q are frequently noted in GCs [15][16][17][18]. CIN is involved in focal gene amplifications as well as to chromosomal gains and losses.…”