Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem.

Daniel Grammel; Monika Warmuth-Metz; André von Bueren; O André; Marcel Kool; Torsten Pietsch; Hans A Kretzschmar; Stefan Rutkowski; Stefan Rutkowski; Stefan M Pfister; Ulrich Schüller

Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem.

Standard

Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. / Grammel, Daniel; Warmuth-Metz, Monika; von Bueren, André; André, O; Kool, Marcel; Pietsch, Torsten; Kretzschmar, Hans A; Rutkowski, Stefan; Rutkowski, Stefan; Pfister, Stefan M; Schüller, Ulrich.

in: ACTA NEUROPATHOL, Jahrgang 123, Nr. 4, 4, 2012, S. 601-614.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Grammel, D, Warmuth-Metz, M, von Bueren, A, André, O, Kool, M, Pietsch, T, Kretzschmar, HA, Rutkowski, S, Rutkowski, S, Pfister, SM & Schüller, U 2012, 'Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem.', ACTA NEUROPATHOL, Jg. 123, Nr. 4, 4, S. 601-614. <http://www.ncbi.nlm.nih.gov/pubmed/22349907?dopt=Citation>

APA

Grammel, D., Warmuth-Metz, M., von Bueren, A., André, O., Kool, M., Pietsch, T., Kretzschmar, H. A., Rutkowski, S., Rutkowski, S., Pfister, S. M., & Schüller, U. (2012). Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. ACTA NEUROPATHOL, 123(4), 601-614. [4]. http://www.ncbi.nlm.nih.gov/pubmed/22349907?dopt=Citation

Vancouver

Grammel D, Warmuth-Metz M, von Bueren A, André O, Kool M, Pietsch T et al. Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. ACTA NEUROPATHOL. 2012;123(4):601-614. 4.

Bibtex

@article{915a89a885f94082ad5f336445ccccdd,

title = "Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem.",

abstract = "Medulloblastoma is a malignant brain tumor of childhood that comprises at least four molecularly distinct subgroups. We have previously described that cerebellar granule neuron precursors may give rise to the subgroup with a molecular fingerprint of Sonic hedgehog (Shh) signaling. Other recent data indicate that precursor cells within the dorsal brain stem may serve as cellular origins for Wnt-associated medulloblastomas. To see whether Shh-associated medulloblastomas are also able to develop in the dorsal brainstem, we analyzed two lines of transgenic mice with constitutive Shh signaling in hGFAP- and Math1-positive brainstem precursor populations, respectively. Our results show that in both of these lines, medulloblastomas arise from granule neuron precursors of the cochlear nuclei, a derivative of the auditory lower rhombic lip. This region is distinct from derivatives of precerebellar lower rhombic lip where medulloblastomas arise in mice with constitutive-active Wnt signaling. With respect to their histology and the expression of appropriate markers, Shh tumors from the murine cochlear nuclei perfectly resemble human Shh-associated medulloblastomas. Moreover, we find that in a series of 63 human desmoplastic medulloblastomas, 21 (33%) have a very close contact to the cochlear nuclei on MR imaging. In conclusion, we demonstrate that precursors of the murine rhombic lip, which either develop into cerebellar or into cochlear granule neurons, may give rise to Shh-associated medulloblastoma, and this has important implications for the cellular origin of human medulloblastomas.",

keywords = "Animals, Humans, Mice, Magnetic Resonance Imaging, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice, Transgenic, Cell Proliferation, Animals, Newborn, Indoles/diagnostic use, Proteins/genetics, Bacterial Proteins/genetics, Basic Helix-Loop-Helix Transcription Factors/metabolism, Cerebellar Neoplasms/*pathology, Cochlear Nucleus/*pathology, Eye Proteins, Galactosides/diagnostic use, Glial Fibrillary Acidic Protein/genetics, Hedgehog Proteins/genetics/*metabolism, Homeodomain Proteins, Ki-67 Antigen/metabolism, Luminescent Proteins/genetics, Medulloblastoma/*pathology, Paired Box Transcription Factors, Phosphopyruvate Hydratase/metabolism, Receptors, G-Protein-Coupled/genetics, Repressor Proteins, Animals, Humans, Mice, Magnetic Resonance Imaging, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice, Transgenic, Cell Proliferation, Animals, Newborn, Indoles/diagnostic use, Proteins/genetics, Bacterial Proteins/genetics, Basic Helix-Loop-Helix Transcription Factors/metabolism, Cerebellar Neoplasms/*pathology, Cochlear Nucleus/*pathology, Eye Proteins, Galactosides/diagnostic use, Glial Fibrillary Acidic Protein/genetics, Hedgehog Proteins/genetics/*metabolism, Homeodomain Proteins, Ki-67 Antigen/metabolism, Luminescent Proteins/genetics, Medulloblastoma/*pathology, Paired Box Transcription Factors, Phosphopyruvate Hydratase/metabolism, Receptors, G-Protein-Coupled/genetics, Repressor Proteins",

author = "Daniel Grammel and Monika Warmuth-Metz and {von Bueren}, Andr{\'e} and O Andr{\'e} and Marcel Kool and Torsten Pietsch and Kretzschmar, {Hans A} and Stefan Rutkowski and Stefan Rutkowski and Pfister, {Stefan M} and Ulrich Sch{\"u}ller",

year = "2012",

language = "English",

volume = "123",

pages = "601--614",

journal = "ACTA NEUROPATHOL",

issn = "0001-6322",

publisher = "Springer",

number = "4",

}

RIS

TY - JOUR

T1 - Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem.

AU - Grammel, Daniel

AU - Warmuth-Metz, Monika

AU - von Bueren, André

AU - André, O

AU - Kool, Marcel

AU - Pietsch, Torsten

AU - Kretzschmar, Hans A

AU - Rutkowski, Stefan

AU - Pfister, Stefan M

AU - Schüller, Ulrich

PY - 2012

Y1 - 2012

N2 - Medulloblastoma is a malignant brain tumor of childhood that comprises at least four molecularly distinct subgroups. We have previously described that cerebellar granule neuron precursors may give rise to the subgroup with a molecular fingerprint of Sonic hedgehog (Shh) signaling. Other recent data indicate that precursor cells within the dorsal brain stem may serve as cellular origins for Wnt-associated medulloblastomas. To see whether Shh-associated medulloblastomas are also able to develop in the dorsal brainstem, we analyzed two lines of transgenic mice with constitutive Shh signaling in hGFAP- and Math1-positive brainstem precursor populations, respectively. Our results show that in both of these lines, medulloblastomas arise from granule neuron precursors of the cochlear nuclei, a derivative of the auditory lower rhombic lip. This region is distinct from derivatives of precerebellar lower rhombic lip where medulloblastomas arise in mice with constitutive-active Wnt signaling. With respect to their histology and the expression of appropriate markers, Shh tumors from the murine cochlear nuclei perfectly resemble human Shh-associated medulloblastomas. Moreover, we find that in a series of 63 human desmoplastic medulloblastomas, 21 (33%) have a very close contact to the cochlear nuclei on MR imaging. In conclusion, we demonstrate that precursors of the murine rhombic lip, which either develop into cerebellar or into cochlear granule neurons, may give rise to Shh-associated medulloblastoma, and this has important implications for the cellular origin of human medulloblastomas.

AB - Medulloblastoma is a malignant brain tumor of childhood that comprises at least four molecularly distinct subgroups. We have previously described that cerebellar granule neuron precursors may give rise to the subgroup with a molecular fingerprint of Sonic hedgehog (Shh) signaling. Other recent data indicate that precursor cells within the dorsal brain stem may serve as cellular origins for Wnt-associated medulloblastomas. To see whether Shh-associated medulloblastomas are also able to develop in the dorsal brainstem, we analyzed two lines of transgenic mice with constitutive Shh signaling in hGFAP- and Math1-positive brainstem precursor populations, respectively. Our results show that in both of these lines, medulloblastomas arise from granule neuron precursors of the cochlear nuclei, a derivative of the auditory lower rhombic lip. This region is distinct from derivatives of precerebellar lower rhombic lip where medulloblastomas arise in mice with constitutive-active Wnt signaling. With respect to their histology and the expression of appropriate markers, Shh tumors from the murine cochlear nuclei perfectly resemble human Shh-associated medulloblastomas. Moreover, we find that in a series of 63 human desmoplastic medulloblastomas, 21 (33%) have a very close contact to the cochlear nuclei on MR imaging. In conclusion, we demonstrate that precursors of the murine rhombic lip, which either develop into cerebellar or into cochlear granule neurons, may give rise to Shh-associated medulloblastoma, and this has important implications for the cellular origin of human medulloblastomas.

KW - Animals

KW - Humans

KW - Mice

KW - Magnetic Resonance Imaging

KW - Oligonucleotide Array Sequence Analysis

KW - Gene Expression Profiling

KW - Mice, Transgenic

KW - Cell Proliferation

KW - Animals, Newborn

KW - Indoles/diagnostic use

KW - Proteins/genetics

KW - Bacterial Proteins/genetics

KW - Basic Helix-Loop-Helix Transcription Factors/metabolism

KW - Cerebellar Neoplasms/pathology

KW - Cochlear Nucleus/pathology

KW - Eye Proteins

KW - Galactosides/diagnostic use

KW - Glial Fibrillary Acidic Protein/genetics

KW - Hedgehog Proteins/genetics/metabolism

KW - Homeodomain Proteins

KW - Ki-67 Antigen/metabolism

KW - Luminescent Proteins/genetics

KW - Medulloblastoma/pathology

KW - Paired Box Transcription Factors

KW - Phosphopyruvate Hydratase/metabolism

KW - Receptors, G-Protein-Coupled/genetics

KW - Repressor Proteins