Molecular characterization of long‐term survivors of glioblastoma using genome‐ and transcriptome‐wide profiling. Issue 8 (28th March 2014)

• Record Type: Journal Article
• Authors: Reifenberger, Guido; Weber, Ruthild G.; Riehmer, Vera; Kaulich, Kerstin; Willscher, Edith; Wirth, Henry; Gietzelt, Jens; Hentschel, Bettina; Westphal, Manfred; Simon, Matthias; Schackert, Gabriele; Schramm, Johannes; Matschke, Jakob; Sabel, Michael C.; Gramatzki, Dorothee; Felsberg, Jörg; Hartmann, Christian; Steinbach, Joachim P.; Schlegel, Uwe; Wick, Wolfgang; Radlwimmer, Bernhard; Pietsch, Torsten; Tonn, Jörg C.; von Deimling, Andreas; Binder, Hans; Weller, Michael; Loeffler, Markus; for the German Glioma Network
• Is Part Of: International journal of cancer. Volume 135:Issue 8(2014:Oct. 15)
• Page Start: 1822
• Page End: 1831
• Publication Date: 2014-03-28
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28836
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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. To elucidate the molecular aberrations in glioblastomas of long‐term survivors, we performed genome‐ and/or transcriptome‐wide molecular profiling of glioblastoma samples from 94 patients, including 28 long‐term 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 used to characterize molecular aberrations in the distinct survival groups considering established molecular markers such as <italic>isocitrate dehydrogenase 1</italic> or <italic>2 (IDH1/2)</italic> mutations, and <italic>O</italic><sup>6</sup><italic>‐methylguanine DNA methyltransferase</italic> (<italic>MGMT</italic>) promoter methylation. Patients with long‐term survival were younger and more often had <italic>IDH1</italic>/<italic>2</italic>‐mutant and <italic>MGMT</italic>‐methylated tumors. Gene expression profiling revealed over‐representation of a distinct (proneural‐like) expression signature in long‐term survivors that was linked to <italic>IDH1/2</italic> mutation. However, <italic>IDH1/2</italic>‐wildtype glioblastomas from long‐term survivors did not show distinct gene expression profiles and included proneural, classical and mesenchymal glioblastoma subtypes. Genomic imbalances also differed between <italic>IDH1/2</italic>‐mutant and <italic>IDH1/2</italic>‐wildtype tumors, but not between survival groups of <italic>IDH1/2</italic>‐wildtype patients. Thus, our data support an important role for <italic>MGMT</italic> promoter methylation and <italic>IDH1/2</italic> mutation in glioblastoma long‐term survival and corroborate the association of <italic>IDH1/2</italic> mutation with distinct genomic and transcriptional profiles. Importantly, however, <italic>IDH1/2</italic>‐wildtype glioblastomas in our cohort of long‐term survivors lacked distinctive DNA copy number changes and gene expression signatures, indicating that other factors might have been responsible for long survival in this particular subgroup of patients.© 2014 UICC</p> </abstract>