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: | , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2019
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| 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 |
| Summary: | 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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| Item Description: | First published: 16 October 2018 Gesehen am 18.09.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1365-2990 |
| DOI: | 10.1111/nan.12523 |