Targets of gene amplification and overexpression at 17q in gastric cancer.
DNA copy number gains and amplifications at 17q are frequent in gastriccancer, yet systematic analyses of the 17q amplicon have not been performed. In this study, we carried out a comprehensive analysis of copy number and expression levels of 636 chromosome 17-specific genes in gastric cancer by using a custom-made chromosome 17-specific cDNA microarray. Analysis of DNA copy number changes by comparative genomic hybridization on cDNA microarray revealed increased copy numbers of 11 known genes (ERBB2, TOP2A, GRB7, ACLY, PIP5K2B, MPRL45, MKP-L, LHX1, MLN51, MLN64, and RPL27) and seven expressed sequence tags (ESTs) that mapped to 17q12-q21 region. To investigate the genes transcribed at the 17q, we performed gene expression analyses on an identical cDNA microarray. Our expression analysis showed overexpression of 8 genes (ERBB2, TOP2A, GRB2, AOC3, AP2B1, KRT14, JUP, and ITGA3) and two ESTs. Of the commonly amplified transcripts, an uncharacterized EST AA552509 and the TOP2A gene were most frequently overexpressed in 82% of the samples. Additional studies will be initiated to understand the possible biological and clinical significance of these genes in gastric cancer development and progression.
Varis
Asta
A
Department of Medical Genetics, University of Helsinki and Helsinki University Central Hospital, Helsinki 00290, Finland.
Wolf
Maija
M
Monni
Outi
O
Vakkari
Marja-Leena
ML
Kokkola
Arto
A
Moskaluk
Chris
C
Frierson
Henry
H
Powell
Steven M
SM
Knuutila
Sakari
S
Kallioniemi
Anne
A
El-Rifai
Wa'el
W
D015152:Blotting, Northern; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured