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@ARTICLE{Reuss:127371,
author = {D. E. Reuss$^*$ and A. Kratz$^*$ and F. Sahm$^*$ and D.
Capper$^*$ and D. Schrimpf$^*$ and C. Koelsche$^*$ and V.
Hovestadt$^*$ and M. Bewerunge-Hudler$^*$ and D. Jones$^*$
and J. Schittenhelm and M. Mittelbronn$^*$ and E. Rushing
and M. Simon and M. Westphal and A. Unterberg and M.
Platten$^*$ and W. Paulus and G. Reifenberger$^*$ and J.-C.
Tonn and K. Aldape and S. Pfister$^*$ and A. Korshunov$^*$
and M. Weller and C. Herold-Mende and W. Wick$^*$ and S.
Brandner and A. von Deimling$^*$},
title = {{A}dult {IDH} wild type astrocytomas biologically and
clinically resolve into other tumor entities.},
journal = {Acta neuropathologica},
volume = {130},
number = {3},
issn = {1432-0533},
address = {Berlin},
publisher = {Springer},
reportid = {DKFZ-2017-03396},
pages = {407 - 417},
year = {2015},
abstract = {IDH wild type (IDHwt) anaplastic astrocytomas WHO grade III
(AA III) are associated with poor outcome. To address the
possibilities of molecular subsets among astrocytoma or of
diagnostic reclassification, we analyzed a series of 160
adult IDHwt tumors comprising 120 AA III and 40 diffuse
astrocytomas WHO grade II (A II) for molecular hallmark
alterations and established methylation and copy number
profiles. Based on molecular profiles and hallmark
alterations the tumors could be grouped into four major
sets. 124/160 $(78 \%)$ tumors were diagnosed as the
molecular equivalent of conventional glioblastoma (GBM), and
15/160 $(9 \%)$ as GBM-H3F3A mutated (GBM-H3). 13/160
$(8 \%)$ exhibited a distinct methylation profile that was
most similar to GBM-H3-K27, however, lacked the H3F3A
mutation. This group was enriched for tumors of
infratentorial and midline localization and showed a trend
towards a more favorable prognosis. All but one of the 120
IDHwt AA III could be assigned to these three groups. 7
tumors recruited from the 40 A II, comprised a variety of
molecular signatures and all but one were reclassified into
distinct WHO entities of lower grades. Interestingly, TERT
mutations were exclusively restricted to the molecular GBM
$(78 \%)$ and associated with poor clinical outcome.
However, the GBM-H3 group lacking TERT mutations appeared to
fare even worse. Our data demonstrate that most of the
tumors diagnosed as IDHwt astrocytomas can be allocated to
other tumor entities on a molecular basis. The diagnosis of
IDHwt diffuse astrocytoma or anaplastic astrocytoma should
be used with caution.},
keywords = {Biomarkers, Tumor (NLM Chemicals) / Isocitrate
Dehydrogenase (NLM Chemicals) / isocitrate dehydrogenase 2,
human (NLM Chemicals) / IDH1 protein, human (NLM Chemicals)
/ TERT protein, human (NLM Chemicals) / Telomerase (NLM
Chemicals)},
cin = {G380 / B060 / W110 / B062 / G160 / G370 / L101 / L401 /
L701 / L501 / L801},
ddc = {610},
cid = {I:(DE-He78)G380-20160331 / I:(DE-He78)B060-20160331 /
I:(DE-He78)W110-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)G160-20160331 / I:(DE-He78)G370-20160331 /
I:(DE-He78)L101-20160331 / I:(DE-He78)L401-20160331 /
I:(DE-He78)L701-20160331 / I:(DE-He78)L501-20160331 /
I:(DE-He78)L801-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26087904},
doi = {10.1007/s00401-015-1454-8},
url = {https://inrepo02.dkfz.de/record/127371},
}