Article

MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma.

Departments of Pathology and Radiation-Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit-0097, Houston, TX 77030, USA.
Neuro-Oncology (Impact Factor: 5.29). 02/2010; 12(2):116-21. DOI: 10.1093/neuonc/nop020
Source: PubMed

ABSTRACT Hypermethylation of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene has been shown to be associated with improved outcome in glioblastoma (GBM) and may be a predictive marker of sensitivity to alkylating agents. However, the predictive utility of this marker has not been rigorously tested with regard to sensitivity to other therapies, namely radiation. To address this issue, we assessed MGMT methylation status in a cohort of patients with GBM who underwent radiation treatment but did not receive chemotherapy as a component of adjuvant treatment. Formalin-fixed, paraffin-embedded tumor samples from 225 patients with newly diagnosed GBM were analyzed via methylation-specific, quantitative real-time polymerase chain reaction following bisulfite treatment on isolated DNA to assess MGMT promoter methylation status. In patients who received radiotherapy alone following resection, methylation of the MGMT promoter correlated with an improved response to radiotherapy. Unmethylated tumors were twice as likely to progress during radiation treatment. The median time interval between resection and tumor progression of unmethylated tumors was also nearly half that of methylated tumors. Promoter methylation was also found to confer improved overall survival in patients who did not receive adjuvant alkylating chemotherapy. Multivariable analysis demonstrated that methylation status was independent of age, Karnofsky performance score, and extent of resection as a predictor of time to progression and overall survival. Our data suggest that MGMT promoter methylation appears to be a predictive biomarker of radiation response. Since this biomarker has also been shown to predict response to alkylating agents, perhaps MGMT promoter methylation represents a general, favorable prognostic factor in GBM.

0 Followers
 · 
295 Views
  • Source
    Glioma - Exploring Its Biology and Practical Relevance, 11/2011; , ISBN: 978-953-307-379-8
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The era of targeted therapy for glioblastoma has arrived, but results have been modest thus far. This review highlights the challenges inherent to treating glioblastoma with targeted therapy and delves into the complex signaling networks that form the molecular basis of novel therapies. Past failures, current challenges, and future possibilities are discussed in the context of the classic "oncogenic" signaling network, as well as the "nononcogenic" stress response network.
    The Cancer Journal 01/2012; 18(1):32-9. DOI:10.1097/PPO.0b013e3182455187 · 3.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glioblastoma is the most common primary malignant brain tumor in adults and is a challenging disease to treat. The current standard therapy includes maximal safe surgical resection, followed by a combination of radiation and chemotherapy with temozolomide. However, recurrence is quite common, so we continue to search for more effective treatments both for initial therapy and at the time of recurrence. This article will review the current standard of care and recent advances in therapy for newly-diagnosed and recurrent glioblastomas, based on the most authoritative guidelines, the National Cancer Institute's comprehensive cancer database Physician Data Query (PDQ®), and the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology(TM) for central nervous system cancers (V.1.2010), to elucidate the current position and in what direction we are advancing.
    Neurologia medico-chirurgica 01/2010; 50(9):713-9. DOI:10.2176/nmc.50.713 · 0.65 Impact Factor

Preview

Download
2 Downloads
Available from