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Integrated gene copy number and expression microarray analysis of gastric cancer highlights potential target genes.

Abstract：

:We performed an integrated array comparative genomic hybridization (aCGH) and expression microarray analysis of 8 normal gastric tissues and 38 primary tumors, including 25 intestinal and 13 diffuse gastric adenocarcinomas to identify genes whose expression is deregulated in association with copy number alteration. Our aim was also to identify molecular genetic alterations that are specific to particular clinicopathological characteristics of gastric cancer. Distinct molecular genetic profiles were identified for intestinal and diffuse gastric cancers and for tumors obtained from 2 different locations of the stomach. Interestingly, the ERBB2 amplification and gains at 20q13.12-q13.33 almost exclusively discriminated intestinal cancers from the diffuse type. In addition, the 17q12-q25 gain was characteristic to cancers located in corpus and the 20q13.12-q13.13 gain was more common in the antrum. Statistical analysis was performed using integrated copy number and expression data to identify genes showing differential expression associated with a copy number alteration. Genes with the highest statistical significance included ERBB2, MUC1, GRB7, PPP1R1B and PPARBP with concomitant changes in copy number and expression. Immunohistochemical analysis of ERBB2 and MUC1 on a tissue microarray containing 78 independent gastric tissues showed statistically significant differences (p < 0.05 and <0.001) in immunopositivity in the intestinal (31 and 70%) and diffuse subtypes (14 and 41%), respectively. In conclusion, our results demonstrate that intestinal and diffuse type gastric cancers as well as cancers located in different sites of the stomach have distinct molecular profiles which may have clinical value.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Myllykangas S,Junnila S,Kokkola A,Autio R,Scheinin I,Kiviluoto T,Karjalainen-Lindsberg ML,Hollmén J,Knuutila S,Puolakkainen P,Monni O

doi

10.1002/ijc.23574

subject

Has Abstract

pub_date

2008-08-15 00:00:00

pages

817-25

issue

eissn

0020-7136

issn

1097-0215

journal_volume

123

pub_type

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Integrated gene copy number and expression microarray analysis of gastric cancer highlights potential target genes.