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@ARTICLE{Wang:301504,
author = {W. Wang and K. Kumegawa and O. S. Chapman and R. Shiraishi
and Z. Xiao and K. Okonechnikov$^*$ and Y. Sun and S. M.
Pfister$^*$ and W. Feng and N. Uesaka and M. Hoshino and S.
Takahashi and A. Korshunov$^*$ and L. Chavez and R. Maruyama
and D. Kawauchi},
title = {{C}hromatin modification abnormalities by {CHD}7 and
{KMT}2{C} loss promote medulloblastoma progression.},
journal = {Cell reports},
volume = {44},
number = {5},
issn = {2211-1247},
address = {Maryland Heights, MO},
publisher = {Cell Press},
reportid = {DKFZ-2025-01043},
pages = {115673},
year = {2025},
note = {Volume 44, Issue 5, 27 May 2025, 115673},
abstract = {Medulloblastoma (MB), a common malignant pediatric brain
tumor arising in the cerebellum, is characterized by
mutations in chromatin modifiers, highlighting the
significance of chromatin modification abnormalities in its
progression. While animal models have effectively
demonstrated this, a comprehensive evaluation of the
oncogenic potential of these mutations remains incomplete.
In this study, we use CRISPR-mediated gene editing to knock
out chromatin modifier genes mutated in human SHH MB, along
with the Ptch1 gene, in cerebellar granule neuron
progenitors of neonatal mice. This reveals that depletion of
Chd7 and Kmt2c accelerates tumor growth. Multi-layered omics
analysis uncovers that inhibition of the neuronal
differentiation program by chromatin dysregulation is a key
signaling pathway in tumor progression. Additionally, forced
expression of Neurod1, a common target of these chromatin
modifiers, inhibits proliferation and promotes
differentiation. These findings highlight converging
chromatin modification abnormalities from distinct mutations
in Sonic Hedgehog MB and suggest that epigenetic drugs
activating neuronal genes have significant potential as
novel treatments.},
keywords = {CHD7 (Other) / CP: Cancer (Other) / KMT2C (Other) / brain
tumor (Other) / chromatin modifications (Other) /
medulloblastoma (Other) / mouse model (Other)},
cin = {B062 / B300 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)B300-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40393452},
doi = {10.1016/j.celrep.2025.115673},
url = {https://inrepo02.dkfz.de/record/301504},
}