Screening of DNA copy-number aberrations in gastric cancer cell lines by array-based comparative genomic hybridization.
We performed genome-wide screening for deoxyribonucleic acid copy-number aberrations in 31 gastric cancer (GC) cell lines by using custom-made comparative genomic hybridization (CGH)-array. Copy-number gains were frequently detected at 1q, 3q, 5p, 7p, 7q, 8q, 11q, 17q, 20p, 20q, Xp and Xq, and losses at 3p, 4p, 4q, 8p, 9p, 18p and 18q. With respect to histological subtypes, copy-number gains at 1p, 16p, 20p, 20q and 22q, and losses at 8p, 10p, 10q and 18q were significantly frequent in cell lines derived from tumors of the well-differentiated type, whereas copy-number gains at 1q, 7p, 7q, Xp and Xq were frequent in the undifferentiated type. Homozygous deletions were seen at five loci, whereas high-level amplifications were detected in 15 of the 31 GC cell lines; these had occurred at 24 loci, including the segment containing CDK6 (7q21.2). Amplification of that gene had never been reported in GC before. Immunohistochemical studies showed increased levels of CDK6 protein in 54 of the 292 primary GC samples we examined (18.5%). Cytoplasmic localization of CDK6, as well as CDK6 over-expression, was more frequent in well-differentiated GC than in undifferentiated tumors. Nuclear expression of CDK6 was more frequent in early stage GC than in advanced tumors, suggesting that nuclear localization of CDK6 is likely to be a prognostic factor for GC. Taken together, our data indicate that CDK6 might be involved in the pathogenesis of GC and, more generally, that CGH-arrays have a powerful potential for identifying novel cancer-related genetic changes in a variety of tumors.
Takada
Hisashi
H
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510, Japan.
Imoto
Issei
I
Tsuda
Hitoshi
H
Sonoda
Itaru
I
Ichikura
Takashi
T
Mochizuki
Hidetaka
H
Okanoue
Takeshi
T
Inazawa
Johji
J
D000230:Adenocarcinoma / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D018628:Gene Dosage; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases
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