@article{discovery10055666,
           month = {November},
            year = {2018},
          number = {5},
           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},
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
          volume = {136},
           pages = {793--803},
         journal = {Acta Neuropathologica},
          author = {Stichel, D and Ebrahimi, A and Reuss, D and Schrimpf, D and Ono, T and Shirahata, M and Reifenberger, G and Weller, M and H{\"a}nggi, D and Wick, W and Herold-Mende, C and Westphal, M and Brandner, S and Pfister, SM and Capper, D and Sahm, F and von Deimling, A},
        keywords = {7+/10q?, 7+/10?, Astrocytoma, Chromosome 10 loss, Chromosome 7 gain, EGFR amplification, Glioblastoma, Pleomorphic xanthoastrocytoma, TERT promoter mutation},
        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.},
             url = {https://doi.org/10.1007/s00401-018-1905-0},
            issn = {1432-0533}
}