Journal Article

Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities

Brandner, Sebastian, Rushing, Elisabeth, Reifenberger, Guido, Aldape, Kenneth, Sahm, Felix, Schrimpf, Daniel, Tonn, Joerg-Christian, Koelsche, Christian, Reuss, David E., Wick, Wolfgang, Korshunov, Andrey, Mittelbronn, Michel, Westphal, Manfred, Schittenhelm, Jens, Jones, David T. W., Pfister, Stefan M., Kratz, Annekathrin, Platten, Michael, Weller, Michael, Simon, Matthias, Unterberg, Andreas, Herold-Mende, Christel, von Deimling, Andreas, Paulus, Werner, Bewerunge-Hudler, Melanie, Hovestadt, Volker, Capper, David

2015

Overview

IDH wild type ( IDH wt) anaplastic astrocytomas WHO grade III (AA III) are associated with poor outcome. To address the possibilities of molecular subsets among astrocytoma or of diagnostic reclassification, we analyzed a series of 160 adult IDH wt tumors comprising 120 AA III and 40 diffuse astrocytomas WHO grade II (A II) for molecular hallmark alterations and established methylation and copy number profiles. Based on molecular profiles and hallmark alterations the tumors could be grouped into four major sets. 124/160 (78 %) tumors were diagnosed as the molecular equivalent of conventional glioblastoma (GBM), and 15/160 (9 %) as GBM- H3F3A mutated (GBM-H3). 13/160 (8 %) exhibited a distinct methylation profile that was most similar to GBM-H3-K27, however, lacked the H3F3A mutation. This group was enriched for tumors of infratentorial and midline localization and showed a trend towards a more favorable prognosis. All but one of the 120 IDH wt AA III could be assigned to these three groups. 7 tumors recruited from the 40 A II, comprised a variety of molecular signatures and all but one were reclassified into distinct WHO entities of lower grades. Interestingly, TERT mutations were exclusively restricted to the molecular GBM (78 %) and associated with poor clinical outcome. However, the GBM-H3 group lacking TERT mutations appeared to fare even worse. Our data demonstrate that most of the tumors diagnosed as IDH wt astrocytomas can be allocated to other tumor entities on a molecular basis. The diagnosis of IDH wt diffuse astrocytoma or anaplastic astrocytoma should be used with caution.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Analysis / Astrocytoma - classification / Astrocytoma - genetics / Astrocytoma - metabolism / Astrocytoma - pathology / Astrocytomas / Biomarkers, Tumor / Brain cancer / Brain Neoplasms - classification / Brain Neoplasms - genetics / Brain Neoplasms - metabolism / Brain Neoplasms - pathology / Brain research / Cancer research / Cohort Studies / Consortia / Dehydrogenases / DNA Methylation / Glioblastoma - classification / Glioblastoma - genetics / Glioblastoma - metabolism / Glioblastoma - pathology / Humans / Immunohistochemistry / Isocitrate Dehydrogenase - genetics / Medical prognosis / Medical research / Medicine / Medicine & Public Health / Methylation / Middle Aged / Mutation / Neoplasm Grading / Neuropathology / Neurosciences / Neurosurgery / Original Paper / Pathology / Promoter Regions, Genetic / Research centers / Survival Analysis / Telomerase / Telomerase - genetics / Tumors