The role of aberrant DNA methylation in Ewing sarcoma is not completely understood. The methylation status of 503 genes in 52 formalin-fixed paraffin-embedded EWS tumors and 3 EWS cell lines was compared to human mesenchymal stem cell primary cultures (hMSCs) using bead chip methylation analysis. Relative expression of methylated genes was assessed in 5-Aza-2-deoxycytidine-(5-AZA)-treated EWS cell lines and in a cohort of primary EWS samples and hMSCs by gene expression and quantitative RT-PCR. 129 genes demonstrated statistically significant hypermethylation in EWS tumors compared to hMSCs. Thirty-six genes were profoundly methylated in EWS and unmethylated in hMSCs. 5-AZA treatment of EWS cell lines resulted in upregulation of expression of hundreds of genes including 162 that were increased by at least 2-fold. The expression of 19 of 36 candidate hypermethylated genes was increased following 5-AZA. Analysis of gene expression from an independent cohort of tumors confirmed decreased expression of six of nineteen hypermethylated genes (AXL, COL1A1, CYP1B1, LYN, SERPINE1,) andVCAN. Comparing gene expression and DNA methylation analyses proved to be an effective way to identify genes epigenetically regulated in EWS. Further investigation is ongoing to elucidate the role of these epigenetic alterations in EWS pathogenesis.
- DNA Methylation and Gene Expression Profiling of Ewing Sarcoma Primary Tumors Reveal Genes That Are Potential Targets of Epigenetic Inactivation
- Nikul Patel - Department of Quality Control, XBiotech, Inc., Austin, TX 78744, USAJennifer Black - Department of Pathology, Vanderbilt University, Nashville, TN 37232, USAXi Chen - Department of Biostatistics, Vanderbilt University, Nashville, TN 37232, USAA. Mario Marcondes - Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USAWilliam M Grady - Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USAElizabeth R Lawlor - Department of Pediatrics and Pathology, University of Michigan, Ann Arbor, MI 48109, USAScott C Borinstein - Division of Pediatric Hematology-Oncology, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232-6510, USA
- Sarcoma, Vol.2012, pp.1-11
- Miller School of Medicine; UMMG Department of Public Health Sciences Research
- English
- Journal article
- 23024594
- PMC3447379
- 991031613707902976