Title |
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
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Published in |
Acta Neuropathologica, September 2018
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DOI | 10.1007/s00401-018-1905-0 |
Pubmed ID | |
Authors |
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 |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 25% |
Portugal | 1 | 13% |
Spain | 1 | 13% |
Unknown | 4 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 6 | 75% |
Practitioners (doctors, other healthcare professionals) | 2 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 161 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 15 | 9% |
Student > Bachelor | 15 | 9% |
Student > Postgraduate | 14 | 9% |
Student > Doctoral Student | 13 | 8% |
Researcher | 12 | 7% |
Other | 21 | 13% |
Unknown | 71 | 44% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 39 | 24% |
Biochemistry, Genetics and Molecular Biology | 22 | 14% |
Neuroscience | 10 | 6% |
Agricultural and Biological Sciences | 3 | 2% |
Unspecified | 3 | 2% |
Other | 9 | 6% |
Unknown | 75 | 47% |