4.6 Article

Sensitivity to temozolomide in brain tumor initiating cells

Journal

NEURO-ONCOLOGY
Volume 12, Issue 7, Pages 756-760

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/noq032

Keywords

brain tumor stem cells; glioblastoma; MGMT methylation; temozolomide

Funding

  1. Alberta Heritage Foundation for Medical Research
  2. Alberta Cancer Foundation

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Molecular alterations in glioblastoma have the potential to guide treatment. Here, we explore the relationship between temozolomide (TMZ) response and O-6-methylguanine DNA methyltransferase (MGMT) status in brain tumor initiating cells (BTICs). Methylation, expression, and sensitivity were assessed in 20 lines; associations were evaluated by Fisher's exact test. Some BTICs were sensitive. Sensitivity to TMZ was only associated with protein expression (P = .001). There were atypical BTICs including TMZ-resistant lines in which the methylation-specific PCR reaction revealed both methylated and unmethylated bands. BTICs are not uniformly resistant to TMZ; some are sensitive. MGMT status does not predict TMZ response with high precision.

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