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A
genotype of the polymorphic DNA repair gene MGMT is associated with de novo
glioblastoma
Inoue R, Isono M, Abe M, Abe T, Kobayashi H
Department
of Neurosurgery, Oita Medical University, 1-1 Idaigaoka, Hasama, Oita 879-5593,
Japan. ryo@oita-med.ac.jp
Glioblastoma is one of the most malignant tumors in humans.
This tumor is thought to develop as a result of the accumulation of genetic
abnormalities, mainly focused on the loss of heterozygosity on chromosome 10.
O6-methylguanine-DNA methyltransferase (MGMT), which is one of the most
important DNA repair proteins, has also been reported that enzymatic activity,
as well as the methylation status of the promoter region of the MGMT gene,
contributes to the therapeutic response of alkylating agents.
We previously found three allelic variants in the MGMT gene and assayed the
characteristics of these polymorphic proteins.
We designed a case-control study to investigate the role of MGMT genotypic risk
factors for primary brain tumors.
We compared the distributions of MGMT genotypes in primary brain tumors and
normal controls.
The frequencies of MGMT genotypes in examined primary brain tumors were not
different from normal subjects.
However, the combined heterozygote of V1 and a wild allele (V1/W) was frequently
detected in de novo glioblastoma group with significant difference.
Interestingly, among glial tumors, the V1/W genotype was dominantly detected in
the patients with de novo glioblastoma.
This study suggests that the V1/W genotype of the MGMT gene may contribute to
the de novo occurrence of glioblastoma.
PMID: 14669534 [PubMed - in process]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14669534&dopt=Abstract
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