%0 Journal Article
%@ 1432-0533
%A Stichel, D
%A Ebrahimi, A
%A Reuss, D
%A Schrimpf, D
%A Ono, T
%A Shirahata, M
%A Reifenberger, G
%A Weller, M
%A Hänggi, D
%A Wick, W
%A Herold-Mende, C
%A Westphal, M
%A Brandner, S
%A Pfister, SM
%A Capper, D
%A Sahm, F
%A von Deimling, A
%D 2018
%F discovery:10055666
%J Acta Neuropathologica
%K 7+/10q−, 7+/10−, Astrocytoma, Chromosome 10 loss, Chromosome 7 gain, EGFR amplification, Glioblastoma, Pleomorphic xanthoastrocytoma, TERT promoter mutation
%N 5
%P 793-803
%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
%U https://discovery.ucl.ac.uk/id/eprint/10055666/
%V 136
%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.
%Z This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.