Copy number variations are progressively associated with the pathogenesis of colorectal cancer in ulcerative colitis

Marigowda, Shivakumar Bhadravathi and Rotti, Harish and Thanvanthri, Gururajan Vasudevan and Aswath, Balakrishnan and Chakrabarty, Sanjiban and Bhat, Ganesh and Rao, Lakshmi and Pai, Cannanore Ganesh and Satyamoorthy, K (2015) Copy number variations are progressively associated with the pathogenesis of colorectal cancer in ulcerative colitis. World Journal of Gastroenterology, 21 (2). pp. 599-605. ISSN 1007-9327

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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]. Chromosomewise 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 cancerassociated genes. All the samples in the different groupswere microsatellite stable. CONCLUSION: Increasing numbers of CNVs are associated with the progression of UC to CAC, and warrant further detailed exploration.

Item Type: Article
Uncontrolled Keywords: Ulcerative colitis; colorectal cancer; molecular analysis; microsatellite instability; Copy number variations.
Subjects: Medicine > KMC Manipal > Gastroenterology
Life Sciences > MLSC Manipal
Depositing User: KMC Manipal
Date Deposited: 20 Jan 2015 10:29
Last Modified: 20 Jan 2015 10:29

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