O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions

International Journal of Molecular Sciences

Claire Villalva²  Ulrich Cortes²  Michel Wager⁴  Jean-Marc Tourani³  Pierre Rivet¹  Celine Marquant¹  Sebastien Martin¹  Ali G. Turhan² 

[1] Department of Hematology and Oncology, University Hospital of Poitiers, University of Poitiers, Poitiers F-86021, France; E-Mails:;INSERM U935, University of Poitiers, Poitiers F-86021, France; E-Mails:;Department of Medical Oncology, University Hospital of Poitiers, University of Poitiers, Poitiers F-86021, France; E-Mail:;Department of Neurosurgery, University Hospital of Poitiers, University of Poitiers, Poitiers F-86021, France; E-Mail:

关键词: MGMT methylation;    glioma stem-like cells;    temozolomide;    differentiation;   

DOI  :  10.3390/ijms13066983

来源: mdpi

【 摘 要 】

Glioblastoma (GBM) is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ). However, the therapeutic efficacy of this treatment is limited due to tumor recurrence and TMZ resistance. Recently isolated, glioma stem-like cells (GSCs) are thought to represent the population of tumorigenic cells responsible for GBM resistance and recurrence following surgery and chemotherapy. In addition, MGMT (O6-methylguanine-methyltransferase) methylation is considered as one of the principal mechanisms contributing to TMZ sensitivity of GBM. In this study we have isolated GSCs from 10 adult GBM patients and investigated the relationship between MGMT methylation status and Temozolomide (TMZ) sensitivity of these lines grown either in stem-like or differentiation promoting conditions. Sensitivity to TMZ was significantly associated with MGMT methylation status in cells committed to differentiation but not in stem-like cells. In addition, patients harboring highly methylated MGMT promoters had a longer overall survival. These results reveal the importance of the differentiation process when considering the predictive value of MGMT status in GSCs for clinical response to TMZ.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.