Detection of aberrations of ubiquitin-conjugating enzyme E2C gene ( UBE2C) in advanced colon cancer with liver metastases by DNA microarray and two-color FISH

Abstract

Using DNA microarrays, the expression profiles of 1,700 genes in the primary tumor, liver metastases and paired normal tissue obtained from nine patients with advanced colorectal cancer was studied. Twenty genes were upregulated and only one gene was downregulated in the primary tumors. In the liver metastases, 39 genes were upregulated and only three genes were downregulated. There was no significant difference in gene expression between the primary tumors and the liver metastases. The most highly overexpressed gene in both the primary tumors and the liver metastases was the ubiquitin-conjugating enzyme E2C gene ( UBE2C), located at 20q13.1. Additionally, two-color FISH analysis using probes for the region 20q13.1 and the chromosome 20 centromere revealed that amplification at 20q13.1 had occurred in 5 of 10 (50%) colon cancers. Comparison between the levels of gene expression and FISH results revealed that UBE2C expression is significantly changed by amplification at 20q13.1, suggesting genomic amplification as one mechanism of increased UBE2C expression. Our results showing aberrations in levels of gene expression and locus copy number of UBE2C suggest that this gene may play an important role in tumor progression leading to advanced colon cancer with liver metastasis.