Open Access

Somatic mutations in glioblastoma are associated with methylguanine-DNA methyltransferase methylation

  • Authors:
    • Kerrie L. McDonald
    • Tania Tabone
    • Anna K. Nowak
    • Wendy N. Erber
  • View Affiliations

  • Published online on: February 20, 2015     https://doi.org/10.3892/ol.2015.2980
  • Pages: 2063-2067
  • Copyright: © McDonald et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The high level of methylguanine‑DNA methyltransferase (MGMT) in glioblastoma is responsible for resistance to alkylating agents, such as temozolomide (TMZ). In glioblastomas with a methylated MGMT promoter, MGMT deficiency is presumed, resulting in an enhanced effect of TMZ. The aim of the present study was to investigate whether genomic alterations work synergistically with MGMT methylation status and contribute to the response to treatment and overall prognosis in glioblastoma. The current study included a cohort of 35 glioblastoma patients, with MGMT promoter methylation present in 48% of tumors. MGMT methylation was associated with significantly longer median survival (29.0 months) compared with patients without MGMT methylated tumors (12.0 months), as well as longer median time to progression following TMZ treatment (13.2 months, compared with 5.6 months for patients with an unmethylated MGMT status). In addition, somatic variants in hot spot exonic regions of 50 key cancer genes were examined in these glioblastomas. Non‑synonymous mutations in methylated MGMT glioblastomas were four times higher compared with unmethylated MGMT glioblastomas. Furthermore, significantly increased frequencies of mutations in the TP53, CDKN2A, PTEN and PIK3CA genes were detected in MGMT methylated glioblastomas. The relative significance of these mutations, and their contribution to TMZ sensitivity, adjunct to MGMT methylation, require further investigation in a larger cohort.
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May-2015
Volume 9 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
McDonald KL, Tabone T, Nowak AK and Erber WN: Somatic mutations in glioblastoma are associated with methylguanine-DNA methyltransferase methylation. Oncol Lett 9: 2063-2067, 2015
APA
McDonald, K.L., Tabone, T., Nowak, A.K., & Erber, W.N. (2015). Somatic mutations in glioblastoma are associated with methylguanine-DNA methyltransferase methylation. Oncology Letters, 9, 2063-2067. https://doi.org/10.3892/ol.2015.2980
MLA
McDonald, K. L., Tabone, T., Nowak, A. K., Erber, W. N."Somatic mutations in glioblastoma are associated with methylguanine-DNA methyltransferase methylation". Oncology Letters 9.5 (2015): 2063-2067.
Chicago
McDonald, K. L., Tabone, T., Nowak, A. K., Erber, W. N."Somatic mutations in glioblastoma are associated with methylguanine-DNA methyltransferase methylation". Oncology Letters 9, no. 5 (2015): 2063-2067. https://doi.org/10.3892/ol.2015.2980