TY  - JOUR
A1  - Stichel, D
A1  - Ebrahimi, A
A1  - Reuss, D
A1  - Schrimpf, D
A1  - Ono, T
A1  - Shirahata, M
A1  - Reifenberger, G
A1  - Weller, M
A1  - Hänggi, D
A1  - Wick, W
A1  - Herold-Mende, C
A1  - Westphal, M
A1  - Brandner, S
A1  - Pfister, SM
A1  - Capper, D
A1  - Sahm, F
A1  - von Deimling, A
JF  - Acta Neuropathologica
SN  - 1432-0533
UR  - https://doi.org/10.1007/s00401-018-1905-0
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
IS  - 5
SP  - 793
VL  - 136
KW  - 7+/10q?
KW  -  7+/10?
KW  -  Astrocytoma
KW  -  Chromosome 10 loss
KW  -  Chromosome 7 gain
KW  -  EGFR amplification
KW  -  Glioblastoma
KW  -  Pleomorphic xanthoastrocytoma
KW  -  TERT promoter mutation
ID  - discovery10055666
N2  - 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.
EP  - 803
AV  - public
Y1  - 2018/11//
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
ER  -