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
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 al...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
5 September 2018
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| In: |
Acta neuropathologica
Year: 2018, Volume: 136, Issue: 5, Pages: 793-803 |
| ISSN: | 1432-0533 |
| DOI: | 10.1007/s00401-018-1905-0 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s00401-018-1905-0
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| Author Notes: | 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 |
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| 245 | 1 | 0 | |a 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 |c 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 |
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| 520 | |a 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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