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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.

DC Field Value Language
dc.contributor.authorPark, TJ-
dc.contributor.authorHan, SU-
dc.contributor.authorCho, YK-
dc.contributor.authorPaik, WK-
dc.contributor.authorKim, YB-
dc.contributor.authorLim, IK-
dc.date.accessioned2011-08-08T05:07:45Z-
dc.date.available2011-08-08T05:07:45Z-
dc.date.issued2001-
dc.identifier.issn0008-543X-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/3704-
dc.description.abstractBACKGROUND: 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.
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dc.language.isoen-
dc.subject.MESHAdenocarcinoma/secondary-
dc.subject.MESHAdult-
dc.subject.MESHAged-
dc.subject.MESHAged, 80 and over-
dc.subject.MESHCarcinogenicity Tests-
dc.subject.MESHDNA Methylation*-
dc.subject.MESHDisease-Free Survival-
dc.subject.MESHFemale-
dc.subject.MESHGenes, ras*-
dc.subject.MESHHumans-
dc.subject.MESHLymphatic Metastasis-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHMutation-
dc.subject.MESHNeoplasm Staging-
dc.subject.MESHO(6)-Methylguanine-DNA Methyltransferase/genetics*-
dc.subject.MESHPromoter Regions, Genetic/physiology-
dc.subject.MESHStomach Neoplasms/genetics*-
dc.subject.MESHStomach Neoplasms/mortality-
dc.subject.MESHStomach Neoplasms/pathology-
dc.titleMethylation 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.-
dc.typeArticle-
dc.identifier.pmid11753949-
dc.contributor.affiliatedAuthor한, 상욱-
dc.contributor.affiliatedAuthor조, 용관-
dc.contributor.affiliatedAuthor백, 운기-
dc.contributor.affiliatedAuthor김, 영배-
dc.contributor.affiliatedAuthor임, 인경-
dc.type.localJournal Papers-
dc.citation.titleCancer-
dc.citation.volume92-
dc.citation.number11-
dc.citation.date2001-
dc.citation.startPage2760-
dc.citation.endPage2768-
dc.identifier.bibliographicCitationCancer, 92(11):2760-2768, 2001-
dc.identifier.eissn1097-0142-
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
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