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Methylation of O(6)-methylguanine-DNA methyltransferase gene is associated significantly with K-ras mutation, lymph node invasion, tumor staging, and disease free survival in patients with gastric carcinoma.

Authors
Park, TJ; Han, SU; Cho, YK; Paik, WK; Kim, YB; Lim, IK
Citation
Cancer, 92(11):2760-2768, 2001
Journal Title
Cancer
ISSN
0008-543X1097-0142
Abstract
BACKGROUND: O(6)-methylguanine-DNA methyltransferase (MGMT) can remove O(6)alkylG DNA adducts. If they are not removed, then the adducts mispair with T during DNA replication, resulting in G-to-A mutation. Interrelations between MGMT gene inactivation by promoter methylation, K-ras mutation, and clinicopathologic features in patients with gastric carcinoma were studied.



METHODS: Surgically removed tumor tissues from 79 patients were analyzed with MGMT methylation by genomic DNA modification and methylation specific polymerase chain reaction analysis, K-ras mutation by mutant allele specific amplification, TNM classification according to the International Union Against Cancer system, and MGMT protein expression by immunohistochemistry.



RESULTS: MGMT-promoter methylation was found in 18 of 79 tumors. Among those 18 tumors, K-ras mutations were found in 33% and 11% of tumors at codons 12 and 13, respectively, corresponding to 20 times and 7 times greater rates of mutation compared with unmethylated tumors. MGMT methylation was associated significantly with lymph node invasion (P < 0.01), tumor stage (P < 0.03) and 5-year disease free survival (P < 0.02). MGMT protein expression was detected in intestinal metaplasia and adenocarcinoma samples, whereas no expression was detected in normal foveolar cells.



CONCLUSIONS: MGMT-promoter methylation in patients with gastric carcinoma was associated significantly with point mutations of K-ras at codons 12 and 13, lymph node invasion, tumor stage, and disease free survival. These associations indicate a significant role of MGMT methylation during gastric carcinogenesis.
MeSH terms
Adenocarcinoma/secondaryAdultAgedAged, 80 and overCarcinogenicity TestsDNA Methylation*Disease-Free SurvivalFemaleGenes, ras*HumansLymphatic MetastasisMaleMiddle AgedMutationNeoplasm StagingO(6)-Methylguanine-DNA Methyltransferase/genetics*Promoter Regions, Genetic/physiologyStomach Neoplasms/genetics*Stomach Neoplasms/mortalityStomach Neoplasms/pathology
PMID
11753949
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
한, 상욱조, 용관백, 운기김, 영배임, 인경
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