Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression

Beatriz Carvalho(Amsterdam UMC Location VUmc), Cornelis T. Postma(Amsterdam UMC Location VUmc), Sandra Mongera(Amsterdam UMC Location VUmc), Erik Hopmans(Amsterdam UMC Location VUmc), Sharon Diskin(University of Pennsylvania), Mark A. van de Wiel(Vrije Universiteit Amsterdam), Wim Van Criekinge(Ghent University), Olivier Thas(Ghent University), Anja Matthäi(University Hospital Carl Gustav Carus), Miguel A. Cuesta(Amsterdam UMC Location VUmc), J S Terhaar Sive Droste(Amsterdam UMC Location VUmc), Mike E. Craanen(Amsterdam UMC Location VUmc), Evelin Schröck(Carl Gustav Carus-Institut), Bauke Ylstra(Amsterdam UMC Location VUmc), Gerrit A. Meijer(Amsterdam UMC Location VUmc)
Gut
October 1, 2008
Cited by 234Open Access
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Abstract

OBJECTIVE: This study aimed to identify the oncogenes at 20q involved in colorectal adenoma to carcinoma progression by measuring the effect of 20q gain on mRNA expression of genes in this amplicon. METHODS: Segmentation of DNA copy number changes on 20q was performed by array CGH (comparative genomic hybridisation) in 34 non-progressed colorectal adenomas, 41 progressed adenomas (ie, adenomas that present a focus of cancer) and 33 adenocarcinomas. Moreover, a robust analysis of altered expression of genes in these segments was performed by microarray analysis in 37 adenomas and 31 adenocarcinomas. Protein expression was evaluated by immunohistochemistry on tissue microarrays. RESULTS: The genes C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5, mapping at 20q, were significantly overexpressed in carcinomas compared with adenomas as a consequence of copy number gain of 20q. CONCLUSION: This approach revealed C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5 genes to be important in chromosomal instability-related adenoma to carcinoma progression. These genes therefore may serve as highly specific biomarkers for colorectal cancer with potential clinical applications.


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