An Animal Model of MYC-driven Medulloblastoma

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2012 Feb 21

PMID 22340590

Citations 175

Authors

Yanxin Pei

Colin E Moore

Jun Wang

Alok K Tewari

Alexey Eroshkin

Yoon-Jae Cho

Hendrik Witt

Andrey Korshunov

Tracy-Ann Read

Julia L Sun

Earlene M Schmitt

C Ryan Miller

Anne F Buckley

Roger E McLendon

Thomas F Westbrook

Paul A Northcott

Michael D Taylor

Stefan M Pfister

Phillip G Febbo

Robert J Wechsler-Reya

Affiliations

Soon will be listed here.

Abstract

Medulloblastoma (MB) is the most common malignant brain tumor in children. Patients whose tumors exhibit overexpression or amplification of the MYC oncogene (c-MYC) usually have an extremely poor prognosis, but there are no animal models of this subtype of the disease. Here, we show that cerebellar stem cells expressing Myc and mutant Trp53 (p53) generate aggressive tumors following orthotopic transplantation. These tumors consist of large, pleiomorphic cells and resemble human MYC-driven MB at a molecular level. Notably, antagonists of PI3K/mTOR signaling, but not Hedgehog signaling, inhibit growth of tumor cells. These findings suggest that cerebellar stem cells can give rise to MYC-driven MB and identify a novel model that can be used to test therapies for this devastating disease.

Citing Articles

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In-depth inference of transcriptional regulatory networks reveals NPM1 as a therapeutic ribosomal regulator in MYC-amplified medulloblastoma.

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Modulation of Stemness and Differentiation Regulators by Valproic Acid in Medulloblastoma Neurospheres.

Freire N, Herlinger A, Vanini J, Dalmolin M, Fernandes M, Nor C bioRxiv. 2024; .

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MYC-dependent upregulation of the de novo serine and glycine synthesis pathway is a targetable metabolic vulnerability in group 3 medulloblastoma.

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PMID: 39377369 PMC: 11726242. DOI: 10.1093/neuonc/noae179.

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