%0 Journal Article
%A Stichel, Damian
%A Ebrahimi, Azadeh
%A Reuss, David
%A Schrimpf, Daniel
%A Ono, Takahiro
%A Shirahata, Mitsuaki
%A Reifenberger, Guido
%A Weller, Michael
%A Hänggi, Daniel
%A Wick, Wolfgang
%A Herold-Mende, Christel
%A Westphal, Manfred
%A Brandner, Sebastian
%A Pfister, Stefan
%A Capper, David
%A Sahm, Felix
%A von Deimling, Andreas
%T 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.
%J Acta neuropathologica
%V 136
%N 5
%@ 1432-0533
%C Berlin
%I Springer
%M DKFZ-2018-01456
%P 793-803
%D 2018
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30187121
%R 10.1007/s00401-018-1905-0
%U https://inrepo02.dkfz.de/record/137576