title: A genome-wide DNA methylation study in colorectal carcinoma.
abstract: BACKGROUND
  We performed a genome-wide scan of 27,578 CpG loci covering 14,475 genes to identify differentially methylated loci (DML) in colorectal carcinoma (CRC).
  
  
  METHODS
  We used Illumina's Infinium methylation assay in paired DNA samples extracted from 24 fresh frozen CRC tissues and their corresponding normal colon tissues from 24 consecutive diagnosed patients at a tertiary medical center.
  
  
  RESULTS
  We found a total of 627 DML in CRC covering 513 genes, of which 535 are novel DML covering 465 genes. We also validated the Illumina Infinium methylation data for top-ranking genes by non-bisulfite conversion q-PCR-based methyl profiler assay in a subset of the same samples. We also carried out integration of genome-wide copy number and expression microarray along with methylation profiling to see the functional effect of methylation. Gene Set Enrichment Analysis (GSEA) showed that among the major "gene sets" that are hypermethylated in CRC are the sets: "inhibition of adenylate cyclase activity by G-protein signaling", "Rac guanyl-nucleotide exchange factor activity", "regulation of retinoic acid receptor signaling pathway" and "estrogen receptor activity". Two-level nested cross validation showed that DML-based predictive models may offer reasonable sensitivity (around 89%), specificity (around 95%), positive predictive value (around 95%) and negative predictive value (around 89%), suggesting that these markers may have potential clinical application.
  
  
  CONCLUSIONS
  Our genome-wide methylation study in CRC clearly supports most of the previous findings; additionally we found a large number of novel DML in CRC tissue. If confirmed in future studies, these findings may lead to identification of genomic markers for potential clinical application.
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL 60637, USA. kibriya@uchicago.edu
authors.forename: Muhammad G
authors.initials: MG
authors.lastname: Kibriya
authors.forename: Maruf
authors.initials: M
authors.lastname: Raza
authors.forename: Farzana
authors.initials: F
authors.lastname: Jasmine
authors.forename: Shantanu
authors.initials: S
authors.lastname: Roy
authors.forename: Rachelle
authors.initials: R
authors.lastname: Paul-Brutus
authors.forename: Ronald
authors.initials: R
authors.lastname: Rahaman
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dodsworth
authors.forename: Muhammad
authors.initials: M
authors.lastname: Rakibuz-Zaman
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kamal
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
mesh_terms: D000328:Adult; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D004273:DNA, Neoplasm