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@ARTICLE{Robson:142919,
author = {J. P. Robson and M. Remke$^*$ and M. Kool$^*$ and E. Julian
and A. Korshunov$^*$ and S. Pfister$^*$ and G. W. Osborne
and M. D. Taylor and B. Wainwright and B. A. Reynolds},
title = {{I}dentification of {CD}24 as a marker of {P}atched1
deleted medulloblastoma-initiating neural progenitor
cells.l401},
journal = {PLOS ONE},
volume = {14},
number = {1},
issn = {1932-6203},
address = {San Francisco, California, US},
publisher = {PLOS},
reportid = {DKFZ-2019-00547},
pages = {e0210665 -},
year = {2019},
abstract = {High morbidity and mortality are common traits of malignant
tumours and identification of the cells responsible is a
focus of on-going research. Many studies are now reporting
the use of antibodies specific to Clusters of
Differentiation (CD) cell surface antigens to identify
tumour-initiating cell (TIC) populations in neural tumours.
Medulloblastoma is one of the most common malignant brain
tumours in children and despite a considerable amount of
research investigating this tumour, the identity of the
TICs, and the means by which such cells can be targeted
remain largely unknown. Current prognostication and
stratification of medulloblastoma using clinical factors,
histology and genetic profiling have classified this tumour
into four main subgroups: WNT, Sonic hedgehog (SHH), Group 3
and Group 4. Of these subgroups, SHH remains one of the most
studied tumour groups due to the ability to model
medulloblastoma formation through targeted deletion of the
Shh pathway inhibitor Patched1 (Ptch1). Here we sought to
utilise CD antibody expression to identify and isolate TIC
populations in Ptch1 deleted medulloblastoma, and determine
if these antibodies can help classify the identity of human
medulloblastoma subgroups. Using a fluorescence-activated
cell sorted (FACS) CD antibody panel, we identified CD24 as
a marker of TICs in Ptch1 deleted medulloblastoma. CD24
expression was not correlated with markers of astrocytes or
oligodendrocytes, but co-labelled with markers of neural
progenitor cells. In conjunction with CD15, proliferating
CD24+/CD15+ granule cell precursors (GCPs) were identified
as a TIC population in Ptch1 deleted medulloblastoma. On
human medulloblastoma, CD24 was found to be highly expressed
on Group 3, Group 4 and SHH subgroups compared with the WNT
subgroup, which was predominantly positive for CD15,
suggesting CD24 is an important marker of non-WNT
medulloblastoma initiating cells and a potential therapeutic
target in human medulloblastoma. This study reports the use
of CD24 and CD15 to isolate a GCP-like TIC population in
Ptch1 deleted medulloblastoma, and suggests CD24 expression
as a marker to help stratify human WNT tumours from other
medulloblastoma subgroups.},
cin = {L401 / B062 / B300},
ddc = {610},
cid = {I:(DE-He78)L401-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)B300-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30657775},
pmc = {pmc:PMC6338368},
doi = {10.1371/journal.pone.0210665},
url = {https://inrepo02.dkfz.de/record/142919},
}