eprintid: 10055666
rev_number: 27
eprint_status: archive
userid: 608
dir: disk0/10/05/56/66
datestamp: 2018-09-11 16:10:43
lastmod: 2021-09-19 22:22:57
status_changed: 2018-09-11 16:10:43
type: article
metadata_visibility: show
creators_name: Stichel, D
creators_name: Ebrahimi, A
creators_name: Reuss, D
creators_name: Schrimpf, D
creators_name: Ono, T
creators_name: Shirahata, M
creators_name: Reifenberger, G
creators_name: Weller, M
creators_name: Hänggi, D
creators_name: Wick, W
creators_name: Herold-Mende, C
creators_name: Westphal, M
creators_name: Brandner, S
creators_name: Pfister, SM
creators_name: Capper, D
creators_name: Sahm, F
creators_name: von Deimling, A
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
ispublished: pub
subjects: UCH
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
keywords: 7+/10q−, 7+/10−, Astrocytoma, Chromosome 10 loss, Chromosome 7 gain, EGFR amplification, Glioblastoma, Pleomorphic xanthoastrocytoma, TERT promoter mutation
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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.
date: 2018-11
date_type: published
official_url: https://doi.org/10.1007/s00401-018-1905-0
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1582271
doi: 10.1007/s00401-018-1905-0
pii: 10.1007/s00401-018-1905-0
lyricists_name: Brandner, Sebastian
lyricists_id: SBRAN30
actors_name: Stacey, Thomas
actors_id: TSSTA20
actors_role: owner
full_text_status: public
publication: Acta Neuropathologica
volume: 136
number: 5
pagerange: 793-803
event_location: Germany
issn: 1432-0533
citation:        Stichel, D;    Ebrahimi, A;    Reuss, D;    Schrimpf, D;    Ono, T;    Shirahata, M;    Reifenberger, G;                                         ... von Deimling, A; + view all <#>        Stichel, D;  Ebrahimi, A;  Reuss, D;  Schrimpf, D;  Ono, T;  Shirahata, M;  Reifenberger, G;  Weller, M;  Hänggi, D;  Wick, W;  Herold-Mende, C;  Westphal, M;  Brandner, S;  Pfister, SM;  Capper, D;  Sahm, F;  von Deimling, A;   - view fewer <#>    (2018)    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.                   Acta Neuropathologica , 136  (5)   pp. 793-803.    10.1007/s00401-018-1905-0 <https://doi.org/10.1007/s00401-018-1905-0>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10055666/7/Brandner%20ANEU-D-18-00510_R1.pdf