RASSF2 methylation is a strong prognostic marker in younger age patients with Ewing sarcoma

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

Research output: Contribution to journalArticlepeer-review

Abstract

Ras-association domain family of genes consist of 10 members (RASSF1-RASSF10), all containing a Ras-association (RA) domain in either the C- or the N-terminus. Several members of this gene family are frequently methylated in common sporadic cancers; however, the role of the RASSF gene family in rare types of cancers, such as bone cancer, has remained largely uninvestigated. In this report, we investigated the methylation status of RASSF1A and RASSF2 in Ewing sarcoma (ES). Quantitative real-time methylation analysis (MethyLight) demonstrated that both genes were frequently methylated in Ewing sarcoma tumors (52.5% and 42.5%, respectively) as well as in ES cell lines and gene expression was upregulated in methylated cell lines after treatment with 5-aza-2′-deoxcytidine. Overexpression of either RASSF1A or RASSF2 reduced colony formation ability of ES cells. RASSF2 methylation correlated with poor overall survival (p = 0.028) and this association was more pronounced in patients under the age of 18 y (p = 0.002). These results suggest that both RASSF1A and RASSF2 are novel epigenetically inactivated tumor suppressor genes in Ewing sarcoma and RASSF2 methylation may have prognostic implications for ES patients.

Original languageEnglish
Pages (from-to)893-898
Number of pages6
JournalEpigenetics
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 2013

Keywords

  • Ewing sarcoma
  • Methylation
  • RASSF1A
  • RASSF2
  • Survival

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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