Epigenetic inactivation of the RASSF1A tumour suppressor gene in ependymoma

Hamilton, David W.; Lusher, Meryl E.; Lindsey, Janet C.; Ellison, David W.; Clifford, Steven C.

doi:10.1016/j.canlet.2004.11.044

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Volume 227, Issue 1 , Pages 75-81, 8 September 2005

Epigenetic inactivation of the RASSF1A tumour suppressor gene in ependymoma

Northern Institute for Cancer Research, Paul O'Gorman Building, The Medical School, University of Newcastle, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK

Received 20 October 2004; received in revised form 26 November 2004; accepted 28 November 2004.

Abstract

To investigate the role of aberrant epigenetic events in ependymoma and identify critical genes in its pathogenesis, the methylation status of nine tumour suppressor genes (TSGs: p14(ARF), p15(INK4B), p16(INK4A), CASP8, MGMT, TIMP3, TP73, RB1 and RASSF1A) was assessed. Extensive hypermethylation across the RASSF1A CpG island was detected frequently in ependymomas of all clinical and pathological disease subtypes (86% of cases, n=35), but not in non-neoplastic brain tissues (n=6). Less frequent methylation was observed for CASP8, MGMT and TP73 (5–20%). The remaining TSGs showed no evidence of methylation. RASSF1A hypermethylation represents the most common gene-specific defect identified in ependymoma highlighting the importance of its further investigation in this disease.