Pharmacogenetic Research of MGMT in brain tumor patients.

• Project/Area Number: 09671428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Oita medical university (1998); Kyushu University (1997)
• Principal Investigator: MORI Teruaki (1998) Oita Medical University, Faculty of Medicine, Assistant Prof., 医学部, 助教授 (60124632); 鈴木 友和 (1997) 九州大学, 生体防御医学研究所, 教授 (20028517)
• Co-Investigator(Kenkyū-buntansha): 森 照明 大分医科大学, 医学部, 助教授 (60124632) ; 鈴木 康代 九州大学, 生体防御医学研究所, 助手 (90226564) ; 阿部 眞佐子 九州大学, 生体防御医学研究所, 助手 (30222665)
• Project Period (FY): 1997 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥2,700,000 (Direct Cost: ¥2,700,000); Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000); Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Pharmacogenetics / Brain tumor / chemotherapy / MGMT / Polymorphism / genotyping / DNA repaireneyme / 遺伝的多型 / 遺伝子型タイピング

Research Abstract

1) O^6-methylguanine-DNA methyltransferase (MGMT) is one of the DNA repair enzymes in mammals. We previously screened the variant alleles for the MGMT gene in the general population, and found three variants (Vi, V2, V3), two of which caused amino acid substitutions (Leu84 Phe for Vi, and Trp65Cys for V2). In order to accelerate the ecogenetic and pharmacogenetic studies on MGMT polymorphism, we developed a new PCR-based RFLP method for genotyping.
2) By using POR-SSCP and POR-RFLP methods, we performed the MGMT genotyping of the patients of brain tumor. The combined heterozygote of wild and V1 MGMT was predominantly detected in the pateints harboring glioblastoma with statistically significance.
3) From the results of the various examination to reveal the characters of human polymorphic MGMTs, we concluded that wild type and Vi protein have similar enzymatic and physicochemical properties, while V2 protein is considered tobe unstable and hardly exists in vivo.

Research Products

• [Publications] Abe M et al.: "A convenient method for genotyping of human O^6-methyl guanine-DNA methyltransterase polymorphism" Jpn J Human Genet. 42・3. 425-428 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Abe M et al.: "A convenient method for genotyping of human O^6-methyl gusnine-DNA methyltraus ferase poly morphism." Jpn J Human Genet.42-3. 425-428 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Abe M et al.: "A convenient method for genotyping of human O^6-methylguanine-DNA methyltransferase polymorphism" Jpn J Human Genet. 42・3. 425-428 (1997)