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O6-Methylguanine-methyltransferase (MGMT) promoter methylation status in glioma stem-like cells is correlated to temozolomide sensitivity under differentiation-promoting conditions.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2012; Vol. 13 (6), pp. 6983-6994. Date of Electronic Publication: 2012 Jun 07. - Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- Aged
Algorithms
Cell Differentiation
Cell Line, Tumor
Dacarbazine analogs & derivatives
Dacarbazine chemistry
Female
Humans
Inhibitory Concentration 50
Male
Microscopy, Confocal
Middle Aged
Sequence Analysis, DNA
Temozolomide
Brain Neoplasms genetics
DNA Methylation
DNA Modification Methylases genetics
DNA Repair Enzymes genetics
Glioma genetics
Neoplastic Stem Cells cytology
Promoter Regions, Genetic
Tumor Suppressor Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 13
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 22837675
- Full Text :
- https://doi.org/10.3390/ijms13066983