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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 (
EGFR
amp), the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10−), and
TERT
promoter mutation (p
TERT
mut) are alterations frequently observed in adult
IDH
-wild-type (
IDH
wt) glioblastoma (GBM). In the absence of endothelial proliferation and/or necrosis, these alterations currently are considered to serve as a surrogate for upgrading
IDH
wt diffuse or anaplastic astrocytoma to GBM. Here, we set out to determine the distribution of
EGFR
amp, 7+/10−, and p
TERT
mut 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
EGFR
amp and the 7/10 signature are closely associated with
IDH
wt GBM. In contrast, p
TERT
mut is less specific for
IDH
wt GBM. We conclude that, in the absence of endothelial proliferation and/or necrosis, the detection of
EGFR
amp is a very strong surrogate marker for the diagnosis of GBM in
IDH
wt diffuse astrocytic tumors. The 7/10 signature is also a strong surrogate marker. However, care should be taken to exclude pleomorphic xanthoastrocytoma. p
TERT
mut is less restricted to this entity and needs companion analysis by other molecular markers to serve as a surrogate for diagnosing
IDH
wt GBM. A combination of any two of
EGFR
amp, the 7/10 signature and p
TERT
mut, is highly specific for
IDH
wt GBM and the combination of all three alterations is frequent and exclusively seen in
IDH
wt GBM.