Low MGMT digital expression is associated with a better outcome of IDH1 wildtype glioblastomas treated with temozolomide

Introduction Glioblastoma (GBM) is the deadliest primary brain tumor. The standard treatment consists of surgery, radiotherapy, and temozolomide (TMZ). TMZ response is heterogeneous, and MGMT promoter ( MGMTp ) methylation has been the major predictive biomarker. We aimed to describe the clinical an...

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Published in:Journal of neuro-oncology 2021, Vol.151 (2), p.135-144
Main Authors: Gomes, Isabella, Moreno, Daniel Antunes, dos Reis, Mariana Bisarro, da Silva, Luciane Sussuchi, Leal, Letícia Ferro, Gonçalves, Gisele Melo, Pereira, Caio Augusto, Oliveira, Marco Antônio, de Medeiros Matsushita, Marcus, Reis, Rui Manuel
Format: Article
Language:English
Subjects:
Brain cancer
Brain tumors
DNA damage
DNA methylation
DNA repair
Gene expression
Glioblastoma
Immunohistochemistry
Laboratory Investigation
Medicine
Medicine & Public Health
Mutation
Neurology
Oncology
Patients
Radiation therapy
Surgery
Temozolomide
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Summary:Introduction Glioblastoma (GBM) is the deadliest primary brain tumor. The standard treatment consists of surgery, radiotherapy, and temozolomide (TMZ). TMZ response is heterogeneous, and MGMT promoter ( MGMTp ) methylation has been the major predictive biomarker. We aimed to describe the clinical and molecular data of GBMs treated with TMZ, compare MGMT methylation with MGMT expression, and further associate with patient’s outcome. Methods We evaluate 112 FFPE adult GBM cases. IDH1 and ATRX expression was analyzed by immunohistochemistry, hotspot TERT promoter ( TERTp ) mutations were evaluated by Sanger or pyrosequencing, and MGMTp methylation was assessed by pyrosequencing and MGMT mRNA expression using the nCounter® Vantage 3D™ DNA damage and repair panel. Results Of the 112 GBMs, 96 were IDH1 WT , and 16 were IDH1 MUT . Positive ATRX expression was found in 91.6% (88/96) of IDH WT and 43.7% (7/16) of IDH MUT . TERTp mutations were detected in 70.4% (50/71) of IDH WT . MGMTp methylation was found in 55.5% (35/63) of IDH WT and 84.6% (11/13) of IDH MUT , and as expected, MGMTp methylation was significantly associated with a better response to TMZ. MGMT expression was inversely correlated with MGMTp methylation levels (− 0.506, p 
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-020-03675-6