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Cytogenet Genome Res. 2007;118(2-4):214-21.

SNP-Array genotyping and spectral karyotyping reveal uniparental disomy as early mutational event in MSS- and MSI-colorectal cancer cell lines.

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1
Department of Medicine II, Division of Gastroenterology, University of Wurzburg, Wurzburg, Germany. melcher_r@klinik.uni-wuerzburg.de

Abstract

In this study nine colorectal cancer cell lines were analysed by 10K SNP-arrays and spectral karyotyping (SKY). Complex chromosomal alterations and breakpoints of deleted or translocated fragments found by SKY could further be characterized by SNP-array analysis. Interestingly many monoallelic regions identified by SNP-array analysis display no copy number alterations, representing uniparental disomy (UPD). It was demonstrated that UPD seems to be involved in activation of early-acting tumor suppressor genes in MSS- (APC, CDKN2A) and MSI- (MLH1, MSH2, APC, CDKN2A) colorectal cancer cell lines. Genes involved later on in the adenoma-carcinoma sequence (i.e. TP53/SMAD4) were not found to be inactivated by UPD. Furthermore, identified amplified monoallelic regions may include oncogenes activated by allele-specific-amplification (i.e. Cyclin D1). However, at present, the majority of the monoallelic regions located in the present study have not yet been associated with known tumor suppressor genes and oncogenes. Further studies are warranted to identify relevant genes in the respective regions and to further verify the results presented here.

PMID:
18000373
DOI:
10.1159/000108303
[Indexed for MEDLINE]
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