Details

Autor(en) / Beteiligte

• KOOS, Björn
• BENDER, Sebastian
• HASSELBLATT, Martin
• WITT, Hendrik
• MERTSCH, Sonja
• FELSBERG, Jörg
• BESCHORNER, Rudi
• KORSHUNOV, Andrey
• RIESMEIER, Barbara
• PFISTER, Stefan
• PAULUS, Werner

Titel

The Transcription Factor Evi-1 Is Overexpressed, Promotes Proliferation, and Is Prognostically Unfavorable in Infratentorial Ependymomas

Ist Teil von

• Clinical cancer research, 2011-06, Vol.17 (11), p.3631-3637

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2011

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Ependymomas are glial tumors of presumably radial glial origin that share morphologic similarities with ependymal cells. The molecular genetics of ependymomas of supratentorial, infratentorial, and spinal location is heterogeneous. We aimed at identifying pathways operative in the development of infratentorial ependymomas. To do so, gene expression profiles of tumor cells laser microdissected from infratentorial ependymomas (n = 15) were compared with that of nonneoplastic ependymal cells laser microdissected from autopsy tissue (n = 7). Among 31 genes significantly overexpressed (>5-fold) in ependymomas, transcription factor EVI1 (ecotropic viral integration site 1) showed the highest overexpression (35-fold). Evi-1 protein expression could be confirmed in formalin-fixed, paraffin-embedded samples of 26 of 28 infratentorial ependymomas but only in 7 of 47 nonependymal glial tumors (P < 0.001). Furthermore, MDS1/EVI1 fusion transcripts were detectable in 17 of 28 infratentorial ependymomas and significantly correlated with MGMT (O6-methylguanine-DNA-methyltransferase) promoter hypermethylation (P < 0.05). In primary infratentorial ependymoma cells, transfection with EVI1-specific siRNAs resulted in significant growth inhibition [48 hours: 87% ± 2% and 74% ± 10% as compared with control (mean ± SD; P < 0.001)]. The prognostic role of EVI1 could further be validated in an independent cohort of 39 infratentorial and 26 supratentorial ependymomas on the basis of mRNA expression profiling. Although in supratentorial ependymomas EVI1 expression status had no prognostic impact, in infratentorial ependymomas, high EVI1 expression was associated with shorter overall survival and progression-free survival. To conclude, the transcription factor Evi-1 is overexpressed in infratentorial ependymomas, promotes proliferation of ependymal tumor cells, and is prognostically unfavorable.