PT  - JOURNAL ARTICLE
AU  - Rachel Michaelson-Cohen
AU  - Ilana Keshet
AU  - Ravid Straussman
AU  - Merav Hecht
AU  - Howard Cedar
AU  - Uziel Beller
TI  - Genome-Wide De Novo Methylation in Epithelial Ovarian Cancer
AID  - 10.1097/IGC.0b013e31820e5cda
DP  - 2011 Jan 01
TA  - International Journal of Gynecologic Cancer
PG  - 269--279
VI  - 21
IP  - 2
4099  - http://ijgc.bmj.com/content/21/2/269.short
4100  - http://ijgc.bmj.com/content/21/2/269.full
SO  - Int J Gynecol Cancer2011 Jan 01; 21
AB  - 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.Objectives: 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.