Cerebellar stem cells act as medulloblastoma-initiating cells in a mouse model and a neural stem cell signature characterizes a subset of human medulloblastomas
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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, Reto; Shakhova, O; Bhagat, Harivadan; Behesti, H; Sutter, Christian; Penkar, S; Santuccione, A C; Bernays, R; Heppner, F L; Schüller, U; Grotzer, M A; Moch, H; Schraml, P; Marino, S.
In: ONCOGENE, Vol. 29, No. 12, 25.03.2010, p. 1845-56.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cerebellar stem cells act as medulloblastoma-initiating cells in a mouse model and a neural stem cell signature characterizes a subset of human medulloblastomas
AU - Sutter, Reto
AU - Shakhova, O
AU - Bhagat, Harivadan
AU - Behesti, H
AU - Sutter, Christian
AU - Penkar, S
AU - Santuccione, A C
AU - Bernays, R
AU - Heppner, F L
AU - Schüller, U
AU - Grotzer, M A
AU - Moch, H
AU - Schraml, P
AU - Marino, S
PY - 2010/3/25
Y1 - 2010/3/25
N2 - 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.
AB - 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.
KW - Animals
KW - Cerebellar Neoplasms
KW - Cerebellum
KW - Disease Models, Animal
KW - Genes, Retinoblastoma
KW - Genes, Tumor Suppressor
KW - Genes, p53
KW - Humans
KW - Intermediate Filament Proteins
KW - Medulloblastoma
KW - Mice
KW - Nerve Tissue Proteins
KW - Nestin
KW - Neurons
KW - SOX9 Transcription Factor
KW - SOXB1 Transcription Factors
KW - Stem Cells
KW - Treatment Failure
KW - Treatment Outcome
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/onc.2009.472
DO - 10.1038/onc.2009.472
M3 - SCORING: Journal article
C2 - 20062081
VL - 29
SP - 1845
EP - 1856
JO - ONCOGENE
JF - ONCOGENE
SN - 0950-9232
IS - 12
ER -