Published online Jan 14, 2015. doi: 10.3748/wjg.v21.i2.616
Peer-review started: March 12, 2014
First decision: April 2, 2014
Revised: May 10, 2014
Accepted: July 22, 2014
Article in press: July 22, 2014
Published online: January 14, 2015
AIM: To evaluate the association of known copy number variations (CNVs) in ulcerative colitis (UC) progressing to colorectal cancer.
METHODS: Microsatellite instability analysis using the National Cancer Institute’s panel of markers, and CNV association studies using Agilent 2 × 105 k arrays were done in tissue samples from four patient groups with UC: those at low risk (LR) or high risk of developing colorectal cancer, those with premalignant dysplastic lesions, and those with colitis-associated colorectal cancer (CAC). DNA from tissue samples of these groups were independently hybridized on arrays and analyzed. The data obtained were further subjected to downstream bioinformatics enrichment analysis to examine the correlation with CAC progression.
RESULTS: Microarray analysis highlighted a progressive increase in the total number of CNVs [LR (n = 178) vs CAC (n = 958), 5.3-fold], gains and losses [LR (n = 37 and 141) vs CAC (n = 495 and 463), 13.4- and 3.3-fold, respectively], size [LR (964.2 kb) vs CAC (10540 kb), 10.9-fold] and the number of genes in such regions [LR (n = 119) vs CAC (n = 455), 3.8-fold]. Chromosome-wise analysis of CNVs also showed an increase in the number of CNVs across each chromosome. There were 38 genes common to all four groups in the study; 13 of these were common to cancer genes from the Genetic Disease Association dataset. The gene set enrichment analysis and ontology analysis highlighted many cancer-associated genes. All the samples in the different groups were microsatellite stable.
CONCLUSION: Increasing numbers of CNVs are associated with the progression of UC to CAC, and warrant further detailed exploration.
Core tip: Ulcerative colitis (UC) confers an increased risk of colorectal cancer (CRC). The role of copy number variations (CNVs) in different cancers including sporadic CRC has been established but their association in the development of colitis-associated neoplasia is not well described. Reports to date are limited to only a particular stage (e.g., dysplasia or cancer) in the development of colitis-associated cancer. In this first study of its kind, we report the association of increased numbers of known CNVs with the progression of UC to colitis-associated cancer.