Source:http://linkedlifedata.com/resource/pubmed/id/12964042
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2003-9-9
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| pubmed:abstractText |
Most sporadic gastric cancer with the microsatellite instability (MSI) phenotype is linked with hypermethylation (HM) of hMLH1. However, a part of gastric cancer with hMLH1 HM does not show MSI, suggesting a region-specific effect of hMLH1 promoter methylation on developing MSI. To test this possibility, we measured the methylation level in 3 distinct areas of hMLH1 promoter and compared them with MSI in 129 sporadic gastric cancer patients. Three areas of hMLH1 promoter, from distal toward proximal, were designated as hMLH1-A, hMLH1-B, and hMLH1-C, respectively. The methylation level was measured by fluorescence-based real-time methylation specific PCR. MSI status was tested using a panel of 5 microsatellite markers (BAT25, BAT26, D2S123, D5S346, and D17S250). Gastric cancers with no HM in hMLH1-A (n=105, 81.4%) also showed no HM in 2 other regions of hMLH1 promoter. On the other hand, the cancers with HM in hMLH1-A (n=24, 18.6%) showed various levels of methylation in 2 other regions. In most cases, the methylation value was the highest in hMLH1-A and the lowest in hMLH1-C. We found the MSI phenotype in 12 cancers (13%) of 92 tested cases and these cancers were all associated with HM in the region of hMLH1-C. A third of hypermethylated cancers in the hMLH1-A region did not show the MSI phenotype. The survival of the patients with HM in hMLH1-C was significantly better than that of patients without HM (P<0.05). These results suggest that HM in the proximal region of hMLH1 promoter, hMLH1-C in this study, plays a critical role in the progression of gastric cancer with MSI. The complete association between HM in hMLH1-C and MSI phenotype with gastric cancer provides an alternative diagnostic tool for detecting a favorable prognostic subgroup with MSI by using simple methylation analysis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MLH1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1107-3756
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
12
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
603-8
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:12964042-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12964042-Adult,
pubmed-meshheading:12964042-Aged,
pubmed-meshheading:12964042-Aged, 80 and over,
pubmed-meshheading:12964042-Carrier Proteins,
pubmed-meshheading:12964042-Cell Line, Tumor,
pubmed-meshheading:12964042-DNA Methylation,
pubmed-meshheading:12964042-Disease Progression,
pubmed-meshheading:12964042-Female,
pubmed-meshheading:12964042-Humans,
pubmed-meshheading:12964042-Male,
pubmed-meshheading:12964042-Microsatellite Repeats,
pubmed-meshheading:12964042-Middle Aged,
pubmed-meshheading:12964042-Neoplasm Proteins,
pubmed-meshheading:12964042-Neoplasms,
pubmed-meshheading:12964042-Nuclear Proteins,
pubmed-meshheading:12964042-Phenotype,
pubmed-meshheading:12964042-Polymerase Chain Reaction,
pubmed-meshheading:12964042-Promoter Regions, Genetic,
pubmed-meshheading:12964042-Stomach Neoplasms,
pubmed-meshheading:12964042-Time Factors
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| pubmed:year |
2003
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| pubmed:articleTitle |
Microsatellite instability in gastric cancer is closely associated with hMLH1 hypermethylation at the proximal region of the promoter.
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| pubmed:affiliation |
Department of Surgery, Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa 920-8641, Japan.
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| pubmed:publicationType |
Journal Article
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