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

Bhadravathi Marigowda Shivakumar, Harish Rotti, Thanvanthri Gururajan Vasudevan, Aswath Balakrishnan, Sanjiban Chakrabarty, Ganesh Bhat, Lakshmi Rao, Cannanore Ganesh Pai, Kapaettu Satyamoorthy

Research output: Contribution to journalArticle

12 Citations (Scopus)

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]. 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 groups CONCLUSION: Increasing numbers of CNVs are associated with the progression of UC to CAC, and warrant further detailed exploration.

Original languageEnglish
Pages (from-to)616-622
Number of pages7
JournalWorld Journal of Gastroenterology
Volume21
Issue number2
DOIs
Publication statusPublished - 14-01-2015

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Ulcerative Colitis
Colorectal Neoplasms
Genes
Microsatellite Instability
Inborn Genetic Diseases
National Cancer Institute (U.S.)
Neoplasm Genes
Colitis
Microarray Analysis
Computational Biology
Chromosomes
DNA

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

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title = "Copy number variations are progressively associated with the pathogenesis of colorectal cancer in ulcerative colitis",
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]. 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 groups CONCLUSION: Increasing numbers of CNVs are associated with the progression of UC to CAC, and warrant further detailed exploration.",
author = "Shivakumar, {Bhadravathi Marigowda} and Harish Rotti and Vasudevan, {Thanvanthri Gururajan} and Aswath Balakrishnan and Sanjiban Chakrabarty and Ganesh Bhat and Lakshmi Rao and Pai, {Cannanore Ganesh} and Kapaettu Satyamoorthy",
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Copy number variations are progressively associated with the pathogenesis of colorectal cancer in ulcerative colitis. / Shivakumar, Bhadravathi Marigowda; Rotti, Harish; Vasudevan, Thanvanthri Gururajan; Balakrishnan, Aswath; Chakrabarty, Sanjiban; Bhat, Ganesh; Rao, Lakshmi; Pai, Cannanore Ganesh; Satyamoorthy, Kapaettu.

In: World Journal of Gastroenterology, Vol. 21, No. 2, 14.01.2015, p. 616-622.

Research output: Contribution to journalArticle

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AU - Shivakumar, Bhadravathi Marigowda

AU - Rotti, Harish

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AU - Chakrabarty, Sanjiban

AU - Bhat, Ganesh

AU - Rao, Lakshmi

AU - Pai, Cannanore Ganesh

AU - Satyamoorthy, Kapaettu

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N2 - 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 groups CONCLUSION: Increasing numbers of CNVs are associated with the progression of UC to CAC, and warrant further detailed exploration.

AB - 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 groups CONCLUSION: Increasing numbers of CNVs are associated with the progression of UC to CAC, and warrant further detailed exploration.

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