Tunc F Ersoy1,2, Vera C Keil3, Dariusch R Hadizadeh4, Gerrit H Gielen5, Rolf Fimmers6, Andreas Waha5, Barbara Heidenreich7, Rajiv Kumar7, Hans H Schild4, Matthias Simon1,2. 1. Department of Neurosurgery and Stereotaxy, University Hospital Bonn, Sigmund-Freud Straße 25, D-53105, Bonn, Germany. 2. Ev. Krankenhaus Bielefeld, Department of Neurosurgery, Kantensiek 11, D-33617, Bielefeld, Germany. 3. Department of Radiology, University Hospital Bonn, Sigmund-Freud Straße 25, D-53105, Bonn, Germany. vera.keil@ukbonn.de. 4. Department of Radiology, University Hospital Bonn, Sigmund-Freud Straße 25, D-53105, Bonn, Germany. 5. Institute of Neuropathology, University Hospital Bonn, Sigmund-Freud Straße 25, D-53105, Bonn, Germany. 6. IMBIE, University Hospital Bonn, Sigmund-Freud Straße 25, D-53105, Bonn, Germany. 7. DFKZ, Department of Molecular Genetic Epidemiology, Im Neuenheimer Feld 280, 69121, Heidelberg, Germany.
Abstract
PURPOSE: Magnetic resonance (MR) imaging biomarkers can assist in the non-invasive assessment of the genetic status in glioblastomas (GBMs). Telomerase reverse transcriptase (TERT) promoter mutations are associated with a negative prognosis. This study was performed to identify MR imaging biomarkers to forecast the TERT mutation status. METHODS: Pre-operative MRIs of 64/67 genetically confirmed primary GBM patients (51/67 TERT-mutated with rs2853669 polymorphism) were analyzed according to Visually AcceSAble Rembrandt Images (VASARI) ( https://wiki.cancerimagingarchive.net/display/Public/VASARI+Research+Project ) imaging criteria by three radiological raters. TERT mutation and O6-methylguanine-DNA methyltransferase (MGMT) hypermethylation data were obtained through direct and pyrosequencing as described in a previous study. Clinical data were derived from a prospectively maintained electronic database. Associations of potential imaging biomarkers and genetic status were assessed by Fisher and Mann-Whitney U tests and stepwise linear regression. RESULTS: No imaging biomarkers could be identified to predict TERT mutational status (alone or in conjunction with TERT promoter polymorphism rs2853669 AA-allele). TERT promoter mutations were more common in patients with tumor-associated seizures as first symptom (26/30 vs. 25/37, p = 0.07); these showed significantly smaller tumors [13.1 (9.0-19.0) vs. 24.0 (16.6-37.5) all cm3; p = 0.007] and prolonged median overall survival [17.0 (11.5-28.0) vs. 9.0 (4.0-12.0) all months; p = 0.02]. TERT-mutated GBMs were underrepresented in the extended angularis region (p = 0.03), whereas MGMT-methylated GBMs were overrepresented in the corpus callosum (p = 0.03) and underrepresented temporomesially (p = 0.01). CONCLUSION: Imaging biomarkers for prediction of TERT mutation status remain weak and cannot be derived from the VASARI protocol. Tumor-associated seizures are less common in TERT mutated glioblastomas.
PURPOSE: Magnetic resonance (MR) imaging biomarkers can assist in the non-invasive assessment of the genetic status in glioblastomas (GBMs). Telomerase reverse transcriptase (TERT) promoter mutations are associated with a negative prognosis. This study was performed to identify MR imaging biomarkers to forecast the TERT mutation status. METHODS: Pre-operative MRIs of 64/67 genetically confirmed primary GBM patients (51/67 TERT-mutated with rs2853669 polymorphism) were analyzed according to Visually AcceSAble Rembrandt Images (VASARI) ( https://wiki.cancerimagingarchive.net/display/Public/VASARI+Research+Project ) imaging criteria by three radiological raters. TERT mutation and O6-methylguanine-DNA methyltransferase (MGMT) hypermethylation data were obtained through direct and pyrosequencing as described in a previous study. Clinical data were derived from a prospectively maintained electronic database. Associations of potential imaging biomarkers and genetic status were assessed by Fisher and Mann-Whitney U tests and stepwise linear regression. RESULTS: No imaging biomarkers could be identified to predict TERT mutational status (alone or in conjunction with TERT promoter polymorphism rs2853669 AA-allele). TERT promoter mutations were more common in patients with tumor-associated seizures as first symptom (26/30 vs. 25/37, p = 0.07); these showed significantly smaller tumors [13.1 (9.0-19.0) vs. 24.0 (16.6-37.5) all cm3; p = 0.007] and prolonged median overall survival [17.0 (11.5-28.0) vs. 9.0 (4.0-12.0) all months; p = 0.02]. TERT-mutated GBMs were underrepresented in the extended angularis region (p = 0.03), whereas MGMT-methylated GBMs were overrepresented in the corpus callosum (p = 0.03) and underrepresented temporomesially (p = 0.01). CONCLUSION: Imaging biomarkers for prediction of TERT mutation status remain weak and cannot be derived from the VASARI protocol. Tumor-associated seizures are less common in TERT mutated glioblastomas.
Authors: Benjamin M Ellingson; Timothy F Cloughesy; Whitney B Pope; Taryar M Zaw; Heidi Phillips; Shadi Lalezari; Phioanh L Nghiemphu; Hassana Ibrahim; Kourosh M Naeini; Robert J Harris; Albert Lai Journal: Neuroimage Date: 2011-10-07 Impact factor: 6.556
Authors: David N Louis; Arie Perry; Guido Reifenberger; Andreas von Deimling; Dominique Figarella-Branger; Webster K Cavenee; Hiroko Ohgaki; Otmar D Wiestler; Paul Kleihues; David W Ellison Journal: Acta Neuropathol Date: 2016-05-09 Impact factor: 17.088
Authors: Jérôme Kroonen; Jessica Nassen; Yves-Gautier Boulanger; Fabian Provenzano; Valérie Capraro; Vincent Bours; Didier Martin; Manuel Deprez; Pierre Robe; Bernard Rogister Journal: Int J Cancer Date: 2010-11-23 Impact factor: 7.396
Authors: Roger Stupp; Monika E Hegi; Warren P Mason; Martin J van den Bent; Martin J B Taphoorn; Robert C Janzer; Samuel K Ludwin; Anouk Allgeier; Barbara Fisher; Karl Belanger; Peter Hau; Alba A Brandes; Johanna Gijtenbeek; Christine Marosi; Charles J Vecht; Karima Mokhtari; Pieter Wesseling; Salvador Villa; Elizabeth Eisenhauer; Thierry Gorlia; Michael Weller; Denis Lacombe; J Gregory Cairncross; René-Olivier Mirimanoff Journal: Lancet Oncol Date: 2009-03-09 Impact factor: 41.316
Authors: Whitney B Pope; Jenny H Chen; Jun Dong; Marc R J Carlson; Alla Perlina; Timothy F Cloughesy; Linda M Liau; Paul S Mischel; Phioanh Nghiemphu; Albert Lai; Stanley F Nelson Journal: Radiology Date: 2008-10 Impact factor: 11.105
Authors: Maximilian Diehn; Christine Nardini; David S Wang; Susan McGovern; Mahesh Jayaraman; Yu Liang; Kenneth Aldape; Soonmee Cha; Michael D Kuo Journal: Proc Natl Acad Sci U S A Date: 2008-03-24 Impact factor: 11.205