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

作者: Björn Koos , Sebastian Bender , Hendrik Witt , Sonja Mertsch , Jörg Felsberg

DOI: 10.1158/1078-0432.CCR-11-0175

关键词:

摘要: Purpose: Ependymomas are glial tumors of presumably radial origin that share morphologic similarities with ependymal cells. The molecular genetics ependymomas supratentorial, infratentorial, and spinal location is heterogeneous. We aimed at identifying pathways operative in the development infratentorial ependymomas. Experimental Design: To do so, gene expression profiles tumor cells laser microdissected from ( n = 15) were compared nonneoplastic autopsy tissue 7). Results: Among 31 genes significantly overexpressed (>5-fold) ependymomas, transcription factor EVI1 (ecotropic viral integration site 1) showed highest overexpression (35-fold). Evi-1 protein could be confirmed formalin-fixed, paraffin-embedded samples 26 28 but only 7 47 nonependymal P MDS1/EVI1 fusion transcripts detectable 17 correlated MGMT (O6-methylguanine-DNA-methyltransferase) promoter hypermethylation -specific siRNAs resulted significant growth inhibition [48 hours: 87% ± 2% 74% 10% as control (mean SD; further validated an independent cohort 39 supratentorial on basis mRNA profiling. Although status had no prognostic impact, high was associated shorter overall survival progression-free survival. Conclusions: conclude, promotes proliferation cells, prognostically unfavorable. Clin Cancer Res; 17(11); 3631–7. ©2011 AACR .

参考文章(28)
David N. Louis, WHO classification of tumours of the central nervous system International Agency for Research on Cancer. ,(2007)
B. Koos, S. Peetz-Dienhart, B. Riesmeier, M. C. Frühwald, M. Hasselblatt, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is significantly less frequent in ependymal tumours as compared to malignant astrocytic gliomas: Scientific correspondence Neuropathology and Applied Neurobiology. ,vol. 36, pp. 356- 358 ,(2010) , 10.1111/J.1365-2990.2010.01077.X
Seiichi Shimizu, Takao Kodera, Kazuhiro Morishita, Hideaki Mizoguchi, Hiroshi Kazama, Ecotropic viral integration site-1 is activated during, and is sufficient for, neuroectodermal P19 cell differentiation. Cell Growth & Differentiation. ,vol. 10, pp. 565- 573 ,(1999)
J Soderholm, H Kobayashi, C Mathieu, JD Rowley, G Nucifora, The leukemia-associated gene MDS1/EVI1 is a new type of GATA-binding transactivator. Leukemia. ,vol. 11, pp. 352- 358 ,(1997) , 10.1038/SJ.LEU.2400584
Sanne Lugthart, Maria E. Figueroa, Eric Bindels, Lucy Skrabanek, Peter J. M. Valk, Yushan Li, Stefan Meyer, Claudia Erpelinck-Verschueren, John Greally, Bob Löwenberg, Ari Melnick, Ruud Delwel, Aberrant DNA hypermethylation signature in acute myeloid leukemia directed by EVI1 Blood. ,vol. 117, pp. 234- 241 ,(2011) , 10.1182/BLOOD-2010-04-281337
Robert A Johnson, Karen D Wright, Helen Poppleton, Kumarasamypet M Mohankumar, David Finkelstein, Stanley B Pounds, Vikki Rand, Sarah ES Leary, Elsie White, Christopher Eden, Twala Hogg, Paul Northcott, Stephen Mack, Geoffrey Neale, Yong-Dong Wang, Beth Coyle, Jennifer Atkinson, Mariko DeWire, Tanya A Kranenburg, Yancey Gillespie, Jeffrey C Allen, Thomas Merchant, Fredrick A Boop, Robert A Sanford, Amar Gajjar, David W Ellison, Michael D Taylor, Richard G Grundy, Richard J Gilbertson, None, Cross-species genomics matches driver mutations and cell compartments to model ependymoma Nature. ,vol. 466, pp. 632- 636 ,(2010) , 10.1038/NATURE09173
E. Bouffet, N. Foreman, Chemotherapy for intracranial ependymomas Childs Nervous System. ,vol. 15, pp. 563- 570 ,(1999) , 10.1007/S003810050544
Susumu Goyama, Mineo Kurokawa, Evi-1 as a critical regulator of leukemic cells International Journal of Hematology. ,vol. 91, pp. 753- 757 ,(2010) , 10.1007/S12185-010-0618-5
Iacopo Sardi, Valentina Cetica, Maura Massimino, Anna Maria Buccoliero, Laura Giunti, Lorenzo Genitori, Maurizio Aricò, Promoter methylation and expression analysis of MGMT in advanced pediatric brain tumors Oncology Reports. ,vol. 22, pp. 773- 779 ,(2009) , 10.3892/OR_00000499
Jacques Guyotat, Philippe Metellus, Roch Giorgi, Marylin Barrie, Anne Jouvet, Michelle Fevre-Montange, Olivier Chinot, Anne Durand, Dominique Figarella-Branger, Infratentorial ependymomas: prognostic factors and outcome analysis in a multi-center retrospective series of 106 adult patients. Acta Neurochirurgica. ,vol. 151, pp. 947- 960 ,(2009) , 10.1007/S00701-009-0417-Z