TY - JOUR
T1 - Influence of Intratumor Heterogeneity on the Predictivity of MGMT Gene Promoter Methylation Status in Glioblastoma
AU - Brigliadori, Giovanni
AU - Goffredo, Giulia
AU - Bartolini, Daniela
AU - Tosatto, Luigino
AU - Gurrieri, Lorena
AU - Mercatali, Laura
AU - Ibrahim, Toni
N1 - Publisher Copyright:
© Copyright © 2020 Brigliadori, Goffredo, Bartolini, Tosatto, Gurrieri, Mercatali and Ibrahim.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/20
Y1 - 2020/10/20
N2 - Glioblastoma is the most aggressive tumor of the central nervous system. Prognosis is poor, even in the presence of a methylated state of MGMT gene promoter, which represents the biomarker with the highest prognostic/predictive value for the standard treatment of patients. Among patients with a methylated MGMT status, we identified an intermediate range of methylation above the standard 9% cut-off (gray zone) in which the predictive strength of the marker was lost. In an effort to improve the evaluation of the biomarker in clinical decision-making, we are carrying out a retrospective study, performing an in-depth analysis of samples used for diagnosis to understand how molecular heterogeneity, a hallmark of glioblastoma, impacts the evaluation of MGMT gene promoter methylation. Preliminary data from samples belonging to the “gray zone” tend to confirm the hypothesis of a mismatch between methylation values used for clinical decision-making and those included in our in-depth analysis. Confirmation of these data would help to better define the predictive power of MGMT promoter methylation status and greatly facilitate clinical decision-making.
AB - Glioblastoma is the most aggressive tumor of the central nervous system. Prognosis is poor, even in the presence of a methylated state of MGMT gene promoter, which represents the biomarker with the highest prognostic/predictive value for the standard treatment of patients. Among patients with a methylated MGMT status, we identified an intermediate range of methylation above the standard 9% cut-off (gray zone) in which the predictive strength of the marker was lost. In an effort to improve the evaluation of the biomarker in clinical decision-making, we are carrying out a retrospective study, performing an in-depth analysis of samples used for diagnosis to understand how molecular heterogeneity, a hallmark of glioblastoma, impacts the evaluation of MGMT gene promoter methylation. Preliminary data from samples belonging to the “gray zone” tend to confirm the hypothesis of a mismatch between methylation values used for clinical decision-making and those included in our in-depth analysis. Confirmation of these data would help to better define the predictive power of MGMT promoter methylation status and greatly facilitate clinical decision-making.
KW - glioblastoma
KW - intratumor heterogeneity
KW - MGMT methylation
KW - predictivity
KW - temozolamide
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U2 - 10.3389/fonc.2020.533000
DO - 10.3389/fonc.2020.533000
M3 - Article
AN - SCOPUS:85095415414
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
SN - 2234-943X
M1 - 533000
ER -