Molecular dissection of the chromosome band 7q21 amplicon in gastroesophageal junction adenocarcinomas identifies cyclin-dependent kinase 6 at both genomic and protein expression levels
Autor: | H. W. Tilanus, M. van Duin, Kees J. Vissers, Josiane C. Wink, R. van Marion, H. van Dekken, Winand N.M. Dinjens, Wim C. J. Hop |
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Přispěvatelé: | Pathology, Epidemiology, Surgery, Hematology |
Rok vydání: | 2008 |
Předmět: |
Cancer Research
Esophageal Neoplasms Locus (genetics) Adenocarcinoma Proto-Oncogene Mas SDG 3 - Good Health and Well-being Stomach Neoplasms Proto-Oncogene Proteins Gene duplication Genetics medicine Humans Receptors Growth Factor biology Contig Hepatocyte Growth Factor Gene Expression Profiling Gene Amplification Cyclin-Dependent Kinase 6 Proto-Oncogene Proteins c-met Amplicon medicine.disease Molecular biology Neoplasm Proteins Gene expression profiling Cancer research biology.protein Esophagogastric Junction Cyclin-dependent kinase 6 Chromosomes Human Pair 7 Comparative genomic hybridization |
Zdroj: | Genes Chromosomes & Cancer, 47(8), 649-656. Wiley-Liss Inc. |
ISSN: | 1098-2264 1045-2257 |
Popis: | Amplification of chromosome band 7q21 has been frequently detected in various types of cancer including gastroesophageal junction (GEJ) adenocarcinomas. At present, no gene has been disclosed that can explain this frequent amplification of 7q21 in GEJ carcinomas. Therefore, a detailed genomic analysis of the 7q21 region was performed on a selected series of GEJ adenocarcinomas, i.e., 14 primary adenocarcinomas and 10 cell lines, by array comparative genomic hybridization (aCGH) with a 7q11.22-q31.2 contig array. A distinct peak of amplification was identified at 92.1 Mb in 7q21.2, precisely comprising cyclin-dependent kinase 6 (CDK6), a gene involved in cell cycle regulation. A smaller peak was seen at 116.2 Mb in 7q31.2, the locus of the MET proto-oncogene. No distinct peak was detected for the hepatocyte growth factor (HGF) at 81.3 Mb in 7q21.11. An immunoprofile of HGF CDK6 and MET revealed a strong correlation between aCGH and immunohistochemical protein expression for CDK6 (P = 0.002). Furthermore, immunohistochemistry did not show expression of CDK6 in Barrett's dysplasia and carcinoma in situ, correlating expression of CDK6 with a malignant phenotype. We conclude that high-resolution genomic analysis and immunoprofiling identify CDK6 as the main candidate target for the recurrent amplification of 7q21 in GEJ adenocarcinomas. (C) 2008 Wiley-Liss, Inc. |
Databáze: | OpenAIRE |
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