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

2008; BMJ; Volume: 58; Issue: 1 Linguagem: Inglês

10.1136/gut.2007.143065

1468-3288

Beatriz Carvalho, Cornelis T. Postma, Sandra Mongera, Erik Hopmans, Sharon Diskin, Mark A. van de Wiel, Wim Van Criekinge, Olivier Thas, Anja Matthäi, Miguel A. Cuesta, J S Terhaar Sive Droste, Mike E. Craanen, Evelin Schröck, Bauke Ylstra, Gerrit A. Meijer,

Cancer Genomics and Diagnostics

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.