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Cerebellar stem cells act as medulloblastoma-initiating cells in a mouse model and a neural stem cell signature characterizes a subset of human medulloblastomas

Sutter, R. and Shakhova, O. and Bhagat, H. and Behesti, H. and Sutter, C. and Penkar, S. and Santuccione, A. and Bernays, R. and Heppner, F. L. and Schüller, U. and Grotzer, M. and Moch, H. and Schraml, P. and Marino, S.. (2010) Cerebellar stem cells act as medulloblastoma-initiating cells in a mouse model and a neural stem cell signature characterizes a subset of human medulloblastomas. Oncogene, Vol. 29, H. 12. pp. 1845-1856.

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Official URL: http://edoc.unibas.ch/dok/A6005677

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Abstract

Cells with stem cell properties have been isolated from various areas of the postnatal mammalian brain, most recently from the postnatal mouse cerebellum. We show here that inactivation of the tumor suppressor genes Rb and p53 in these endogenous neural stem cells induced deregulated proliferation and resistance to apoptosis in vitro. Moreover, injection of these cells into mice formed medulloblastomas. Medulloblastomas are the most common malignant brain tumors of childhood, and despite recent advances in treatment they are associated with high morbidity and mortality. They are highly heterogeneous tumors characterized by a diverse genetic make-up and expression profile as well as variable prognosis. Here, we describe a novel ontogenetic pathway of medulloblastoma that significantly contributes to understanding their heterogeneity. Experimental medulloblastomas originating from neural stem cells preferentially expressed stem cell markers Nestin, Sox2 and Sox9, which were not expressed in medulloblastomas originating from granule-cell-restricted progenitors. Furthermore, the expression of these markers identified a subset of human medulloblastomas associated with a poorer clinical outcome.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
UniBasel Contributors:Schraml, Peter Hans
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Macmillan
ISSN:0950-9232
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:13 Sep 2013 07:56
Deposited On:24 May 2013 09:20

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