TY  - JOUR
AU  - Stichel, Damian
AU  - Ebrahimi, Azadeh
AU  - Reuss, David
AU  - Schrimpf, Daniel
AU  - Ono, Takahiro
AU  - Shirahata, Mitsuaki
AU  - Reifenberger, Guido
AU  - Weller, Michael
AU  - Hänggi, Daniel
AU  - Wick, Wolfgang
AU  - Herold-Mende, Christel
AU  - Westphal, Manfred
AU  - Brandner, Sebastian
AU  - Pfister, Stefan
AU  - Capper, David
AU  - Sahm, Felix
AU  - von Deimling, Andreas
TI  - 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.
JO  - Acta neuropathologica
VL  - 136
IS  - 5
SN  - 1432-0533
CY  - Berlin
PB  - Springer
M1  - DKFZ-2018-01456
SP  - 793-803
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30187121
DO  - DOI:10.1007/s00401-018-1905-0
UR  - https://inrepo02.dkfz.de/record/137576
ER  -