Mutation and methylation of hMLH1 in gastric carcinomas with microsatellite instability.
World J Gastroenterol
; 9(4): 655-9, 2003 Apr.
Article
em En
| MEDLINE
| ID: mdl-12679904
ABSTRACT
AIM:
To appraise the correlation of mutation and methylation of hMSH1 with microsatellite instability (MSI) in gastric cancers.METHODS:
Mutation of hMLH1 was detected by Two-dimensional electrophoresis (Two-D) and DNA sequencing; Methylation of hMLH1 promoter was measured with methylation-specific PCR; MSI was analyzed by PCR-based methods.RESULTS:
Sixty-eight cases of sporadic gastric carcinoma were studied for mutation and methylation of hMLH1 promoter and MSI. Three mutations were found, two of them were caused by a single bp substitution and one was caused by a 2 bp substitution, which displayed similar Two-D band pattern. Methylation of hMLH1 promoter was detected in 11(16.2 %) gastric cancer. By using five MSI markers, MSI in at least one locus was detected in 17/68(25 %) of the tumors analyzed. Three hMLH1 mutations were all detected in MSI-H (>=2 loci, n=8), but no mutation was found in MSI-L (only one locus, n=9) or MSS (tumor lacking MSI or stable, n=51). Methylation frequency of hMLH1 in MSI-H (87.5 %, 7/8) was significantly higher than that in MSI-L (11.1 %, 1/9) or MSS (5.9 %, 3/51) (P<0.01-0.001), but no difference was found between MSI-L and MSS (P>0.05).CONCLUSION:
Both mutation and methylation of hMLH1 are involved in the MSI pathway but not related to the LOH pathway in gastric carcinogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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DNA de Neoplasias
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Regiões Promotoras Genéticas
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Repetições de Microssatélites
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Mutação
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Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article