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@ARTICLE{Herrlinger:128762,
author = {U. Herrlinger and D. Jones$^*$ and M. Glas and E. Hattingen
and D. Gramatzki and M. Stuplich and J. Felsberg and O.
Bähr and G. H. Gielen and M. Simon and D. Wiewrodt and M.
Schabet and V. Hovestadt$^*$ and D. Capper$^*$ and J. P.
Steinbach and A. von Deimling$^*$ and P. Lichter$^*$ and S.
Pfister$^*$ and M. Weller and G. Reifenberger$^*$},
title = {{G}liomatosis cerebri: no evidence for a separate brain
tumor entity.},
journal = {Acta neuropathologica},
volume = {131},
number = {2},
issn = {1432-0533},
address = {Berlin},
publisher = {Springer},
reportid = {DKFZ-2017-04777},
pages = {309 - 319},
year = {2016},
abstract = {Gliomatosis cerebri (GC) is presently considered a distinct
astrocytic glioma entity according to the WHO classification
for CNS tumors. It is characterized by widespread, typically
bilateral infiltration of the brain involving three or more
lobes. Genetic studies of GC have to date been restricted to
the analysis of individual glioma-associated genes, which
revealed mutations in the isocitrate dehydrogenase 1 (IDH1)
and tumor protein p53 (TP53) genes in subsets of patients.
Here, we report on a genome-wide analysis of DNA methylation
and copy number aberrations in 25 GC patients. Results were
compared with those obtained for 105 patients with various
types of conventional, i.e., non-GC gliomas including
diffuse astrocytic gliomas, oligodendrogliomas and
glioblastomas. In addition, we assessed the prognostic role
of methylation profiles and recurrent DNA copy number
aberrations in GC patients. Our data reveal that the
methylation profiles in 23 of the 25 GC tumors corresponded
to either IDH mutant astrocytoma (n = 6), IDH mutant and
1p/19q codeleted oligodendroglioma (n = 5), or IDH
wild-type glioblastoma including various molecular
subgroups, i.e., H3F3A-G34 mutant (n = 1), receptor
tyrosine kinase 1 (RTK1, n = 4), receptor tyrosine kinase
2 (classic) (RTK2, n = 2) or mesenchymal (n = 5)
glioblastoma groups. Two tumors showed methylation profiles
of normal brain tissue due to low tumor cell content. While
histological grading (WHO grade IV vs. WHO grade II and III)
was not prognostic, the molecular classification as
classic/RTK2 or mesenchymal glioblastoma was associated with
worse overall survival. Multivariate Cox regression analysis
revealed MGMT promoter methylation as a positive prognostic
factor. Taken together, DNA-based large-scale molecular
profiling indicates that GC comprises a genetically and
epigenetically heterogeneous group of diffuse gliomas that
carry DNA methylation and copy number profiles closely
matching the common molecularly defined glioma entities.
These data support the removal of GC as a distinct glioma
entity in the upcoming revision of the WHO classification.},
keywords = {Tumor Suppressor Proteins (NLM Chemicals) / Isocitrate
Dehydrogenase (NLM Chemicals) / IDH1 protein, human (NLM
Chemicals) / DNA Modification Methylases (NLM Chemicals) /
MGMT protein, human (NLM Chemicals) / DNA Repair Enzymes
(NLM Chemicals)},
cin = {L401 / L101 / L501 / B062 / B060 / G380},
ddc = {610},
cid = {I:(DE-He78)L401-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)L501-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)B060-20160331 / I:(DE-He78)G380-20160331},
pnm = {319H - Addenda (POF3-319H)},
pid = {G:(DE-HGF)POF3-319H},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26493382},
doi = {10.1007/s00401-015-1495-z},
url = {https://inrepo02.dkfz.de/record/128762},
}