Novel MYC-driven medulloblastoma models from multiple embryonic cerebellar cells

Oncogene
Daisuke KawauchiMartine F Roussel

Abstract

Group3 medulloblastoma (MBG3) that predominantly occur in young children are usually associated with MYC amplification and/or overexpression, frequent metastasis and a dismal prognosis. Physiologically relevant MBG3 models are currently lacking, making inferences related to their cellular origin thus far limited. Using in utero electroporation, we here report that MBG3 mouse models can be developed in situ from different multipotent embryonic cerebellar progenitor cells via conditional expression of Myc and loss of Trp53 function in several Cre driver mouse lines. The Blbp-Cre driver that targets embryonic neural progenitors induced tumors exhibiting a large-cell/anaplastic histopathology adjacent to the fourth ventricle, recapitulating human MBG3. Enforced co-expression of luciferase together with Myc and a dominant-negative form of Trp53 revealed that GABAergic neuronal progenitors as well as cerebellar granule cells give rise to MBG3 with their distinct growth kinetics. Cross-species gene expression analysis revealed that these novel MBG3 models shared molecular characteristics with human MBG3, irrespective of their cellular origin. We here developed MBG3 mouse models in their physiological environment and we show that oncog...Continue Reading

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Citations

Dec 4, 2019·Brain Pathology·Martine F Roussel, Jennifer L Stripay
Jul 21, 2020·Nature Communications·Jamie ZagozewskiTamra E Werbowetski-Ogilvie
Jan 30, 2018·Molecular Oncology·Margaret StromeckiTamra E Werbowetski-Ogilvie
Jun 9, 2018·Scientific Reports·BaoHan T VoMartine F Roussel
Mar 17, 2019·Journal of Hematology & Oncology·Otília MenyhártBalázs Győrffy
Apr 12, 2018·Annual Review of Neuroscience·Jun WangRobert J Wechsler-Reya
Jan 31, 2020·Nature Communications·Claudio BallabioLuca Tiberi
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Sep 11, 2020·Cancers·Amanda ThomazRafael Roesler
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Apr 20, 2021·Frontiers in Oncology·Zhiqin Li, Sigrid A Langhans
Jun 25, 2021·Science Advances·Claudio BallabioLuca Tiberi

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Datasets Mentioned

BETA
GSE37418
GSE35493
GSE33199
GSE65888

Methods Mentioned

BETA
genetic modifications
fluorescence-activated cell sorting
chip
genotyping
transfection

Software Mentioned

randomForest
R
R2
Bioconductor
CRAN
STATA
ComBat
Partek Genomics Suite
ggplot2
Statistical Parametric Mapping SPM5

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