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.