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Abstract
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, PHF11, 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 PHF11 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.
Disclosure of Potential Conflicts of Interest
The authors declare no conflict of interest.
Acknowledgments
Abdullah Alholle was supported in part by Kuwait Medical Genetics Centre (KMGC), Ministry of Health, Kuwait and funding from University of Birmingham, UK. We would also like to thank Bone Cancer Research Trust and Ministero della Salute of Italy, Ricerca Corrente L2013 for financial support.
Supplemental Materials
Supplemental materials may be found here: www.landesbioscience.com/journals/epigenetics/article/26266