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Integrated molecular characterization of IDH-mutant glioblastomas

Aims: 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...

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Main Authors: Korshunov, Andrey (Author) , Casalini, Belén (Author) , Chavez, Lukas (Author) , Hielscher, Thomas (Author) , Sill, Martin (Author) , Schrimpf, Daniel (Author) , Stichel, Damian (Author) , Capper, David (Author) , Sturm, Dominik (Author) , Lichter, Peter (Author) , Herold-Mende, Christel (Author) , Wick, Wolfgang (Author) , Pfister, Stefan (Author) , Kool, Marcel (Author) , Jones, David T. W. (Author) , Deimling, Andreas von (Author) , Sahm, Felix (Author)
Format: Article (Journal)
Language:English
Published: 2019
In: Neuropathology & applied neurobiology
Year: 2019, Volume: 45, Issue: 2, Pages: 108-118
ISSN:1365-2990
DOI:10.1111/nan.12523
Online Access:Verlag, Volltext: https://doi.org/10.1111/nan.12523
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/nan.12523
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Author Notes:A. Korshunov, B. Casalini, L. Chavez, T. Hielscher, M. Sill, M. Ryzhova, T. Sharma, D. Schrimpf, D. Stichel, D. Capper, D.E. Reuss, D. Sturm, O. Absalyamova, A. Golanov, S. Lambo, M. Bewerunge‐Hudler, P. Lichter, C. Herold‐Mende, W. Wick, S.M. Pfister, M. Kool, D.T.W. Jones, A. von Deimling and F. Sahm

MARC

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500 |a Gesehen am 18.09.2019 
520 |a Aims: 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. Methods: 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. Results: 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. Conclusions: 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. 
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