MOLECULAR GENETIC DETERMINANTS OF LONG-TERM SURVIVAL WITH GLIOBLASTOMA

BACKGROUND: The prognosis of glioblastoma, the most malignant type of glioma, is still poor, with only a minority of patients showing long-term survival of more than three years after diagnosis. We aimed to elucidate the poorly characterized molecular aberrations in glioblastomas of longterm survivo...

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Published in:	Neuro-oncology (Charlottesville, Va.) Vol. 16; no. suppl 3; pp. iii46 - iii47
Main Authors:	Weller, M., Weber, R. G., Riehmer, V., Kaulich, K., Willscher, E., Wirth, H., Gietzelt, J., Hentschel, B., Westphal, M., Simon, M., Schackert, G., Schramm, J., Matschke, J., Sabel, M. C., Gramatzki, D., Felsberg, J., Hartmann, C., Steinbach, J. P., Schlegel, U., Wick, W., Radlwimmer, B., Pietsch, T., Tonn, J. C., von Deimling, A., Binder, H., Loeffler, M., Reifenberger, G.
Format:	Journal Article
Language:	English
Published:	Oxford University Press 01-07-2014
Subjects:	abstracts
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Summary:	BACKGROUND: The prognosis of glioblastoma, the most malignant type of glioma, is still poor, with only a minority of patients showing long-term survival of more than three years after diagnosis. We aimed to elucidate the poorly characterized molecular aberrations in glioblastomas of longterm survivors. METHODS: We performed genome- and/or transcriptome-wide molecular profiling of primary tumor samples from 94 glioblastoma patients of the German Glioma Network, including 28 longterm survivors with >36 months overall survival (OS), 20 short-term survivors with <12 months OS, and 46 patients with intermediate OS. Integrative bioinformatic analyses were performed to characterize molecular aberrations in the distinct survival groups considering established molecular markers such as isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. RESULTS: Patients with long-term survival were younger and more often had IDH1/2-mutant and MGMT promoter-methylated tumors. Gene expression profiling revealed over-representation of a distinct (proneural-like) expression signature in long-term survivors that was linked to IDH1/2 mutation. However, among the IDH1/2-wildtype patients, tumors from long-term survivors did not show distinct gene expression profiles and included proneural, classical and mesenchymal glioblastoma subtypes. Genomic imbalances also differed between IDH1/2-mutant and -wildtype tumors, but not between survival groups of IDH1/2-wildtype patients. CONCLUSIONS: Our data support an important role for MGMT promoter methylation and IDH1/2 mutation in glioblastoma long-term survival and corroborate the association of IDH1/2 mutation with distinct genomic and transcriptional profiles. However, IDH1/2-wildtype glioblastomas from long-term survivors do not carry distinct DNA copy number changes or gene expression signatures, indicating that host factors play a major role in allowing for long-term survival. SECONDARY CATEGORY: Clinical Neuro-Oncology.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1522-8517 1523-5866
DOI:	10.1093/neuonc/nou209.19