TY  - JOUR
AU  - Korshunov, Andrey
AU  - Casalini, B.
AU  - Chavez, L.
AU  - Hielscher, T.
AU  - Sill, M.
AU  - Ryzhova, M.
AU  - Sharma, T.
AU  - Schrimpf, D.
AU  - Stichel, D.
AU  - Capper, D.
AU  - Reuss, D. E.
AU  - Sturm, D.
AU  - Absalyamova, O.
AU  - Golanov, A.
AU  - Lambo, S.
AU  - Bewerunge-Hudler, M.
AU  - Lichter, P.
AU  - Herold-Mende, C.
AU  - Wick, W.
AU  - Pfister, Stefan
AU  - Kool, M.
AU  - Jones, David
AU  - von Deimling, A.
AU  - Sahm, Felix
TI  - Integrated molecular characterization of IDH-mutant glioblastomas.
JO  - Neuropathology & applied neurobiology
VL  - 45
IS  - 2
SN  - 0305-1846
CY  - Oxford [u.a.]
PB  - Wiley-Blackwell
M1  - DKFZ-2019-00668
SP  - 108 - 118
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30326163
DO  - DOI:10.1111/nan.12523
UR  - https://inrepo02.dkfz.de/record/143049
ER  -