Functional epigenetic approach identifies frequently methylated genes in Ewing sarcoma

Abdullah Alholle, Anna T. Brini, Seley Gharanei, Sumathi Vaiyapuri, Elena Arrigoni, Ashraf Dallol, Dean Gentle, Takeshi Kishida, Toru Hiruma, Smadar Avigad, Robert Grimer, Eamonn R. Maher, Farida Latif*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Using a candidate gene approach we recently identified frequent methylation of the RASSF2 gene associated with poor overall survival in Ewing sarcoma (Es). To identify effective biomarkers in Es on a genome-wide scale, we used a functionally proven epigenetic approach, in which gene expression was induced in Es cell lines by treatment with a demethylating agent followed by hybridization onto high density gene expression microarrays. after following a strict selection criterion, 34 genes were selected for expression and methylation analysis in Es cell lines and primary Es. Eight genes (CTHRC1, DNAJA4, ECHDC2, NEFH, NPTX2, P H F 11, RARRES2, TSGA14) showed methylation frequencies of >20% in Es tumors (range 24-71%), these genes were expressed in human bone marrow derived mesenchymal stem cells (hBMsc) and hypermethylation was associated with transcriptional silencing. Methylation of NPTX2 or P H F11 was associated with poorer prognosis in Es. In addition, six of the above genes also showed methylation frequency of >20% (range 36-50%) in osteosarcomas. Identification of these genes may provide insights into bone cancer tumorigenesis and development of epigenetic biomarkers for prognosis and detection of these rare tumor types.

Original languageEnglish
Pages (from-to)1198-1204
Number of pages7
Issue number11
StatePublished - 2013


  • 5-aza-2′-deoxycytidine
  • Bone tumors
  • Ewing sarcoma
  • Functional epigenomics
  • Osteosarcoma


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