Is the absolute value of O(6)-methylguanine-DNA methyltransferase gene messenger RNA a prognostic factor, and does it predict the results of treatment of glioblastoma with temozolomide?

Abstract

OBJECTIVES:

Methylation of O(6)-methylguanine-DNA methyltransferase (MGMT) has been reported to be a good prognostic factor for patients with glioblastoma multiforme (GBM). To determine whether the absolute value of MGMT messenger RNA (mRNA) might be a prognostic factor and useful for predicting the therapeutic effectiveness of temozolomide, especially with regard to GBMs, the authors measured the absolute value of MGMT mRNA in gliomas by using real-time reverse-transcription polymerase chain reaction (RT-PCR).

METHODS:

MGMT mRNA was measured in 140 newly diagnosed gliomas by real-time RT-PCR using the Taq-Man probe. Among 73 GBMs, 45 had been initially treated with temozolomide and radiation.

RESULTS:

The mean MGMT mRNA value was significantly lower in oligodendroglial tumors than in other tumors. In the 73 GBMs, a significant prognostic factor for progression-free survival was fewer than 1000 copies/ μgRNA of MGMT mRNA (p = 0.0150). Of 45 patients with GBMs that had been treated with temozolomide and radiation, progression-free survival was significantly longer for those whose GMB had fewer than 1000 copies/μgRNA of MGMT mRNA than for those whose GBM had more than 1000 copies/μgRNA (p = 0.0090). In 32 patients with GBMs treated by temozolomide and radiation whose age was younger than 75 years and whose Karnofsky Performance Scale score was more than 70, progression-free and overall survival times were longer for those with GBMs of fewer than 5000 copies/μgRNA of MGMT mRNA than for those with GBMs of more than 5000 copies/μgRNA (p = 0.0365 and p = 0.0312).

CONCLUSIONS:

MGMT mRNA might be useful as a prognostic factor and for predicting the results of therapy for GBMs treated by temozolomide. New individual adjuvant therapy based on the results of MGMT mRNA quantitation has been proposed.

• Authors: Satoshi Tanaka, Jiro Akimoto, Yoshitaka Narita, Hidehiro Oka, Takashi Tashiro
• Journal: Journal of neurosurgery (J Neurosurg) Vol. 121 Issue 4 Pg. 818-26 (Oct 2014) ISSN: 1933-0693 [Electronic] United States
• PMID: 25105699 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Alkylating
• RNA, Messenger
• Dacarbazine
• O(6)-Methylguanine-DNA Methyltransferase
• Temozolomide

Topics

• Adult
• Antineoplastic Agents, Alkylating (therapeutic use)
• Brain Neoplasms (chemistry, drug therapy, genetics)
• Dacarbazine (analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Female
• Glioblastoma (chemistry, drug therapy, genetics)
• Humans
• Male
• Middle Aged
• O(6)-Methylguanine-DNA Methyltransferase (genetics)
• Prognosis
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Temozolomide