1998 Fiscal Year Final Research Report Summary
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 Oita Medical University, Faculty of Medicine, Assistant Prof., 医学部, 助教授 (60124632)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Keywords | Pharmacogenetics / Brain tumor / chemotherapy / MGMT / Polymorphism / genotyping / DNA repaireneyme |
|---|
| 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.
|
