%0 Journal Article
%A Korshunov, Andrey
%A Casalini, B.
%A Chavez, L.
%A Hielscher, T.
%A Sill, M.
%A Ryzhova, M.
%A Sharma, T.
%A Schrimpf, D.
%A Stichel, D.
%A Capper, D.
%A Reuss, D. E.
%A Sturm, D.
%A Absalyamova, O.
%A Golanov, A.
%A Lambo, S.
%A Bewerunge-Hudler, M.
%A Lichter, P.
%A Herold-Mende, C.
%A Wick, W.
%A Pfister, Stefan
%A Kool, M.
%A Jones, David
%A von Deimling, A.
%A Sahm, Felix
%T Integrated molecular characterization of IDH-mutant glioblastomas.
%J Neuropathology & applied neurobiology
%V 45
%N 2
%@ 0305-1846
%C Oxford [u.a.]
%I Wiley-Blackwell
%M DKFZ-2019-00668
%P 108 - 118
%D 2019
%X Mutations of isocitrate dehydrogenase (IDH)1/2 affect almost all astrocytomas of WHO grade II and III. A subset of IDH-mutant astrocytic tumours progresses to IDH-mutant glioblastoma or presents with the histology of a glioblastoma at first presentation. We set out here to assess the molecular spectrum of IDH-mutant glioblastomas.We performed an integrated molecular analysis of a mono-centric cohort (n = 97); assessed through genome-wide DNA methylation analysis, copy-number profiling and targeted next generation sequencing using a neurooncology-tailored gene panel.Of these 97 IDH-mutant glioblastomas, 68 had a glioblastoma at first presentation (de novo IDH-mutant glioblastoma) and 29 emerged from a prior low-grade lesion (evolved IDH-mutant glioblastoma). Unsupervised hierarchical clustering of DNA methylation data disclosed that IDH-mutant glioblastoma (de novo and evolved) formed a distinct group separate from other diffuse glioma subtypes. Homozygous deletions of CDKN2A/B were found to be associated with shorter survival.This study demonstrates DNA methylation patterns in IDH-mutant glioblastoma to be distinct from lower-grade astrocytic counterparts but homogeneous within de novo and evolved IDH-mutant glioblastomas, and identifies CDKN2A as a marker for possible genetic sub-stratification.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30326163
%R 10.1111/nan.12523
%U https://inrepo02.dkfz.de/record/143049