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 IDH wt astrocytoma to glioblastoma

AbstractEGFR amplification (EGFRamp), the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10 −), andTERT promoter mutation (pTERTmut) are alterations frequently observed in adultIDH-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 upgradingIDHwt diffuse or anaplastic astrocytoma to GBM. Here, we set out to determine the distribution ofEGFRamp, 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 thatEGFRamp and the 7/10 signature are closely associated withIDHwt GBM. In contrast, pTERTmut is less specific forIDHwt GBM. We conclude that, in the absence of endothelial proliferation and/or necrosis, the detection ofEGFRamp is a very strong surrogate marker for the diagnosis of GBM inIDHwt 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...
Source: Acta Neuropathologica - Category: Neurology Source Type: research