title: Copy number variations are progressively associated with the pathogenesis of colorectal cancer in ulcerative colitis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Increasing numbers of CNVs are associated with the progression of UC to CAC, and warrant further detailed exploration.
authors.affiliation: Bhadravathi Marigowda Shivakumar, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India.
authors.forename: Bhadravathi Marigowda
authors.initials: BM
authors.lastname: Shivakumar
authors.affiliation: Bhadravathi Marigowda Shivakumar, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India.
authors.forename: Harish
authors.initials: H
authors.lastname: Rotti
authors.affiliation: Bhadravathi Marigowda Shivakumar, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India.
authors.forename: Thanvanthri Gururajan
authors.initials: TG
authors.lastname: Vasudevan
authors.affiliation: Bhadravathi Marigowda Shivakumar, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India.
authors.forename: Aswath
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: Bhadravathi Marigowda Shivakumar, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India.
authors.forename: Sanjiban
authors.initials: S
authors.lastname: Chakrabarty
authors.affiliation: Bhadravathi Marigowda Shivakumar, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Bhat
authors.affiliation: Bhadravathi Marigowda Shivakumar, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rao
authors.affiliation: Bhadravathi Marigowda Shivakumar, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India.
authors.forename: Cannanore Ganesh
authors.initials: CG
authors.lastname: Pai
authors.affiliation: Bhadravathi Marigowda Shivakumar, Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576104, India.
authors.forename: Kapaettu
authors.initials: K
authors.lastname: Satyamoorthy
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D019295:Computational Biology; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011230:Precancerous Conditions / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: Colorectal cancer; Copy number variations; Microsatellite instability; Molecular analysis; Ulcerative colitis