Coamplified and overexpressed genes at ERBB2 locus in gastric cancer.
DNA copy number amplification at the chromosomal region of 17q is frequent in gastric cancer. Recently 17q21 was identified as the critical region for the amplicon formation because this region harbors the ERBB2 oncogene and several other targets, such as TOP2A and DARPP32. In our study, we characterized the amplification (52 cases) and expression (29 cases) levels of ERBB2, TOP2A and DARPP32 in gastric cancer samples. These 3 genes were concomitantly amplified in 17% of the intestinal type of gastric adenocarcinoma. However, the expression levels were independent, showing overexpression of DARPP32 (48%), TOP2A (17%) and ERBB2 (3%) studied by quantitative real-time PCR. The most frequently overexpressed gene, DARPP32, exhibited strong protein overexpression in 45% (30/66) of the cases in immunohistochemical study of gastric cancer tumor tissue array. Additional studies are required to thoroughly understand the biological significance of these genes in gastric cancer.
Departments of Pathology and Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital Laboratory Diagnostics, Helsinki, Finland.
Asta
A
Varis
Alexander
A
Zaika
Pauli
P
Puolakkainen
Balint
B
Nagy
Irene
I
Madrigal
Arto
A
Kokkola
Aki
A
Väyrynen
Päivi
P
Kärkkäinen
Christopher
C
Moskaluk
Wa'el
W
El-Rifai
Sakari
S
Knuutila
D000230:Adenocarcinoma / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005753:Gastric Mucosa / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D000075223:Poly-ADP-Ribose Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C000618811:TOP2A protein, human