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Integrated molecular characterization of IDH-mutant glioblastomas.

Authors :: Korshunov A
Casalini B
Chavez L
Hielscher T
Sill M
Ryzhova M
Sharma T
Schrimpf D
Stichel D
Capper D
Reuss DE
Sturm D
Absalyamova O
Golanov A
Lambo S
Bewerunge-Hudler M
Lichter P
Herold-Mende C
Wick W
Pfister SM
Kool M
Jones DTW
von Deimling A
Sahm F
Source :: Neuropathology and applied neurobiology [Neuropathol Appl Neurobiol] 2019 Feb; Vol. 45 (2), pp. 108-118. Date of Electronic Publication: 2018 Nov 15.
Publication Year :: 2019
Abstract: 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.<br />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.<br />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.<br />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.<br /> (© 2018 British Neuropathological Society.)