Chromosome 20q gene signature associated with colorectal cancer progression.

Abstract

Amplification of human chromosome 20q has been reported as the most frequently recurring genetic abnormality associated with large scale changes in mRNA and protein levels in sporadic colorectal carcinomas. While some studies have found 20q amplification to be consistent between primary and metastatic samples from the same patient with a role in the development of metastasis and worse patient prognosis, others have reported association with improved overall survival for a subset of these patients with colorectal cancer (CRC). To fine map the Minimal Common Regions (MCRs) of amplification on chromosome 20q and identify the candidate genes playing roles in progression of the disease, microarray comparative genomic hybridization analyses of two in vitro cultured CRC liver metastasis cell line model systems was utilized. Microarray expression analysis led to the identification of a candidate gene signature comprising of four genes, BMP7, DNMT3B, UBE2C and YWHAB, residing in the MCRs that were over expressed in CRC cells. By validating our results in a training set of 23 adenocarcinomas (tumors) and five adenomas (polyps) using reverse transcription‑quantitative PCR, as well as analyses of two larger colorectal cancer test data sets derived from 195 The Cancer Genome Atlas and 182 MD Anderson Cancer Center patients with colorectal adenocarcinoma patients, this gene signature was ascertained to be associated with lymph node spread and/or distant metastasis (P<0.05). Previously reported functional studies of the gene signature indicated their involvement in inflammatory and immune response pathways driving CRC progression.