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Erschienen in: Acta Neuropathologica 5/2018

05.09.2018 | Original Paper

Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDHwt astrocytoma to glioblastoma

verfasst von: Damian Stichel, Azadeh Ebrahimi, David Reuss, Daniel Schrimpf, Takahiro Ono, Mitsuaki Shirahata, Guido Reifenberger, Michael Weller, Daniel Hänggi, Wolfgang Wick, Christel Herold-Mende, Manfred Westphal, Sebastian Brandner, Stefan M. Pfister, David Capper, Felix Sahm, Andreas von Deimling

Erschienen in: Acta Neuropathologica | Ausgabe 5/2018

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Abstract

EGFR amplification (EGFRamp), the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10−), and TERT promoter mutation (pTERTmut) are alterations frequently observed in adult IDH-wild-type (IDHwt) glioblastoma (GBM). In the absence of endothelial proliferation and/or necrosis, these alterations currently are considered to serve as a surrogate for upgrading IDHwt diffuse or anaplastic astrocytoma to GBM. Here, we set out to determine the distribution of EGFRamp, 7+/10−, and pTERTmut by analyzing high-resolution copy-number profiles and next-generation sequencing data of primary brain tumors. In addition, we addressed the question whether combinations of partial gains on chromosome 7 and partial losses on chromosome 10 exhibited a diagnostic and prognostic value similar to that of complete 7+/10−. Several such combinations proved relevant and were combined as the 7/10 signature. Our results demonstrate that EGFRamp and the 7/10 signature are closely associated with IDHwt GBM. In contrast, pTERTmut is less specific for IDHwt GBM. We conclude that, in the absence of endothelial proliferation and/or necrosis, the detection of EGFRamp is a very strong surrogate marker for the diagnosis of GBM in IDHwt diffuse astrocytic tumors. The 7/10 signature is also a strong surrogate marker. However, care should be taken to exclude pleomorphic xanthoastrocytoma. pTERTmut is less restricted to this entity and needs companion analysis by other molecular markers to serve as a surrogate for diagnosing IDHwt GBM. A combination of any two of EGFRamp, the 7/10 signature and pTERTmut, is highly specific for IDHwt GBM and the combination of all three alterations is frequent and exclusively seen in IDHwt GBM.
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Metadaten
Titel
Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDHwt astrocytoma to glioblastoma
verfasst von
Damian Stichel
Azadeh Ebrahimi
David Reuss
Daniel Schrimpf
Takahiro Ono
Mitsuaki Shirahata
Guido Reifenberger
Michael Weller
Daniel Hänggi
Wolfgang Wick
Christel Herold-Mende
Manfred Westphal
Sebastian Brandner
Stefan M. Pfister
David Capper
Felix Sahm
Andreas von Deimling
Publikationsdatum
05.09.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Acta Neuropathologica / Ausgabe 5/2018
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-018-1905-0

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