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Diagnostic implications of TERT promoter mutation status in diffuse gliomas in a routine clinical setting

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Abstract

IDH (isocitrate dehydrogenase) gene mutations are present in most diffuse low-grade gliomas and define the clinico-pathological core of the respective morphologically defined entities. Conversely, according to the 2016 WHO classification, the majority of glioblastomas belong to the IDH-wildtype category, which is defined by exclusion. TERT (telomerase reverse transcriptase gene) promoter mutations have been suggested as a molecular marker for primary glioblastomas. We analyzed molecular, histopathological, and clinical profiles of a series of 110 consecutive diffuse gliomas (WHO grades II-IV) diagnosed at our institution, in which TERT promoter mutation analysis had been performed as part of diagnostic work-up. A diagnostic algorithm based on IDH, TERT, ATRX, H3F3A, and 1p19q co-deletion status resulted in a consistent molecular classification with only 14 (13%) marker-negative tumors. TERT promoter mutations were present in 77% of IDH-wildtype tumors. The TERT/IDH-wildtype category was highly enriched for tumors with unconventional clinical or histological features. Molecular classes were associated with distinct rates of MGMT promoter methylation. We conclude that, in a routine diagnostic setting, TERT promoter mutations define a relatively homogeneous core group among IDH-wildtype diffuse gliomas that includes the majority of primary glioblastomas as well as their putative precursor lesions.

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Authors and Affiliations

  1. Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland

    Ekkehard Hewer, Nadine Prebil, Sabina Berezowska, Matthias S. Dettmer & Erik Vassella

  2. Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland

    Marielena Gutt-Will & Philippe Schucht

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  1. Ekkehard Hewer
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  2. Nadine Prebil
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Correspondence to Ekkehard Hewer.

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Hewer, E., Prebil, N., Berezowska, S. et al. Diagnostic implications of TERT promoter mutation status in diffuse gliomas in a routine clinical setting. Virchows Arch 471, 641–649 (2017). https://doi.org/10.1007/s00428-017-2216-x

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  • DOI: https://doi.org/10.1007/s00428-017-2216-x

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