Alkylpurine–DNA–N-glycosylase confers resistance to temozolomide in xenograft models of glioblastoma multiforme and is associated with poor survival in patients

Dec 14, 2011The Journal of clinical investigation

DNA Repair Enzyme Linked to Temozolomide Resistance and Poor Survival in Brain Tumor Models and Patients

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Abstract

High nuclear expression of APNG is associated with poorer overall survival in patients with glioblastoma multiforme (GBM).

  • Silencing APNG in TMZ-resistant GBM cell lines reduced DNA damage repair and increased cell death.
  • Reintroducing APNG in TMZ-sensitive GBM lines increased resistance to TMZ in laboratory and mouse models.
  • Coexpression of APNG and MGMT in GBM cells enhanced resistance to TMZ.
  • In clinical datasets, increased APNG promoter methylation was linked to loss of APNG expression in some patients.

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