title: Genome-wide de novo methylation in epithelial ovarian cancer.
abstract: BACKGROUND
  DNA methylation regulates gene expression during development. The methylation pattern is established at the time of implantation. CpG islands are genome regions usually protected from methylation; however, selected islands are methylated later. Many undergo methylation in cancer, causing epigenetic gene silencing. Aberrant methylation occurs early in tumorigenesis, in a specific pattern, inhibiting differentiation.Although methylation of specific genes in ovarian tumors has been demonstrated in numerous studies, they represent only a fraction of all methylated genes in tumorigenesis.
  
  
  OBJECTIVE
  To explore the hypermethylation design in ovarian cancer compared with the methylation profile of normal ovaries, on a genome-wide scale, thus shedding light on the role of gene silencing in ovarian carcinogenesis.Identifying genes that undergo de novo methylation in ovarian cancer may assist in creating biomarkers for disease diagnosis, prognosis, and treatment responsiveness.
  
  
  METHODS
  DNA was collected from human epithelial ovarian cancers and normal ovaries. Methylation was detected by immunoprecipitation using 5-methyl-cytosine-antibodies. DNA was hybridized to a CpG island microarray containing 237,220 gene promoter probes. Results were analyzed by hybridization intensity, validated by bisulfite analysis.
  
  
  RESULTS
  : A total of 367 CpG islands were specifically methylated in cancer cells. There was enrichment of methylated genes in functional categories related to cell differentiation and proliferation inhibition. It seems that their silencing enables tumor proliferation.
  
  
  CONCLUSIONS
  This study provides new perspectives on methylation in ovarian carcinoma, genome-wide. It illustrates how methylation of CpG islands causes silencing of genes that have a role in cell differentiation and functioning. It creates potential biomarkers for diagnosis, prognosis, and treatment responsiveness.
authors.affiliation: Department of Gynecology, Shaare Zedek Medical Center, Israel. rachelmc@szmc.org.il
authors.forename: Rachel
authors.initials: R
authors.lastname: Michaelson-Cohen
authors.forename: Ilana
authors.initials: I
authors.lastname: Keshet
authors.forename: Ravid
authors.initials: R
authors.lastname: Straussman
authors.forename: Merav
authors.initials: M
authors.lastname: Hecht
authors.forename: Howard
authors.initials: H
authors.lastname: Cedar
authors.forename: Uziel
authors.initials: U
authors.lastname: Beller
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D018899:CpG Islands; D019175:DNA Methylation; D020868:Gene Silencing; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics