Shivakumar BM, Rotti H, Vasudevan TG, Balakrishnan A, Chakrabarty S, Bhat G, Rao L, Pai CG, Satyamoorthy K. Copy number variations are progressively associated with the pathogenesis of colorectal cancer in ulcerative colitis. World J Gastroenterol 2015; 21(2): 616-622 [PMID: 25605985 DOI: 10.3748/wjg.v21.i2.616]
Corresponding Author of This Article
Cannanore Ganesh Pai, Professor, Head, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal, Karnataka 576104, India. cgpai@yahoo.co.in
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Clinical Trials Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Bhadravathi Marigowda Shivakumar, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India
Bhadravathi Marigowda Shivakumar, Harish Rotti, Thanvanthri Gururajan Vasudevan, Aswath Balakrishnan, Sanjiban Chakrabarty, Kapaettu Satyamoorthy, School of Life Sciences, Manipal University, Manipal 576104, India
Ganesh Bhat, Cannanore Ganesh Pai, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India
Lakshmi Rao, Department of Pathology, Kasturba Medical College, Manipal University, Manipal 576104, India
Author contributions: Satyamoorthy K and Pai CG conceived the project, along with Shivakumar BM designed the study, collected samples and clinical data; Shivakumar BM, Rotti H and Vasudevan TG were involved in carrying out molecular experiments, analyzing the data and drafting the manuscript; Balakrishnan A and Chakrabarty S were involved in data analysis and interpretation; Pai CG and Bhat G provided the samples; Rao L performed all pathological characterizations; Satyamoorthy K provided support for molecular analysis; all authors read and approved the final manuscript.
Supported by Grants from Department of Biotechnology (BT/01/COE/06/02/07) and TIFAC-CORE in Pharmacogenomics, Government of India.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Cannanore Ganesh Pai, Professor, Head, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal, Karnataka 576104, India. cgpai@yahoo.co.in
Telephone: +91-820-2522385 Fax: +91-820-2571934
Received: March 11, 2014 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 Processing time: 312 Days and 23.2 Hours
Abstract
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.
