Journal Article

DKFZ-2019-00668

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Integrated molecular characterization of IDH-mutant glioblastomas.

Korshunov, A. (First author)DKFZ* ; Casalini, B.DKFZ* ; Chavez, L.DKFZ* ; Hielscher, T.DKFZ* ; Sill, M.DKFZ* ; Ryzhova, M. ; Sharma, T.DKFZ* ; Schrimpf, D.DKFZ* ; Stichel, D.DKFZ* ; Capper, D.DKFZ* ; Reuss, D. E.DKFZ* ; Sturm, D.DKFZ* ; Absalyamova, O. ; Golanov, A. ; Lambo, S.DKFZ* ; Bewerunge-Hudler, M.DKFZ* ; Lichter, P.DKFZ* ; Herold-Mende, C. ; Wick, W.DKFZ* ; Pfister, S.DKFZ* ; Kool, M.DKFZ* ; Jones, D.DKFZ* ; von Deimling, A.DKFZ* ; Sahm, F. (Last author)DKFZ*

2019
Wiley-Blackwell Oxford [u.a.]

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Please use a persistent id in citations: doi:10.1111/nan.12523

Abstract: 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.

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Contributing Institute(s):

1. KKE Neuropathologie (B300)
2. Pädiatrische Neuroonkologie (B062)
3. Biostatistik (C060)
4. Microarray Unit (W110)
5. Molekulare Genetik (B060)
6. KKE Neuroonkologie (B320)
7. DKTK Heidelberg (L101)
8. DKTK Berlin (L201)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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