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Aberrant methylation and reduced expression of RASSF1A in Ewing sarcoma
Author(s) -
Avigad Smadar,
Shukla Shruti,
Naumov Inna,
Cohen Ian J.,
Ash Shifra,
Meller Isaac,
Kollender Yehuda,
Issakov Josephine,
Yaniv Isaac
Publication year - 2009
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22115
Subject(s) - demethylating agent , methylation , cancer research , dna methylation , medicine , context (archaeology) , sarcoma , malignancy , clinical significance , oncology , biology , pathology , gene expression , gene , genetics , paleontology
Background Ewing sarcoma (ES) is the second most common solid bone and soft tissue malignancy in children and young adults with low cure rates indicating the need to identify further prognostic markers. The importance of methylation in the inactivation of key tumor suppressor genes including RASSF1A has begun to be appreciated in context of cancer development, prognosis and therapy. However there is lack of similar broad based studies in ES. The objective of this study was to analyze RASSF1A methylation and assess its clinical significance in ES. Procedure The methylation of RASSF1A was determined 31 ES tumor samples and 4 ES cell lines. ES cell lines were also treated with demethylating agent 5‐aza‐2′‐deoxycytidine to ascertain its effect on methylation. RASSF1A expression was studied in 12 ES tumors. The association between RASSF1A methylation, clinical parameters and outcome was also analyzed. Results Methylation of RASSF1A was observed in 21/31 (68%) tumors and in 3/4 ES cell lines. A significant correlation of methylation to reduced expression of RASSF1A was observed in 12 ES tumors analyzed ( P = 0.0013) and in all cell lines. ES patients with methylated RASSF1A had worse prognosis compared to the unmethylated group ( P = 0.049). Treatment with 5‐aza‐2′‐deoxycytidine resulted in the re‐expression of the unmethylated form of RASSF1A in two ES cell lines. Conclusion RASSF1A is frequently methylated in ES. Pediatr Blood Cancer 2009;53:1023–1028. © 2009 Wiley‐Liss, Inc.