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Article: hMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability

TitlehMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability
Authors
Issue Date1999
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 1999, v. 59 n. 1, p. 159-164 How to Cite?
AbstractMutation of DNA mismatch repair genes has rarely been documented in sporadic gastric carcinoma with microsatellite instability (MSI). In sporadic colorectal carcinoma, hMLH1 promoter methylation associated with protein loss is found in the majority of high-frequency MSI eases. We investigated a series of 35 sporadic gastric carcinomas stratified into high-frequency MSI (MSI-H), low-frequency MSI (MSI-L) and microsatellite stable (MSS) groups and found that hypermethylation of the CpG island in the hMLH1 promoter region was present in 100% of MSI-H sporadic gastric carcinomas. In 90% of cases, there was an associated complete loss of hMLH1 protein, as detected by immunohistochemistry, and a markedly lowered hMLH1 mRNA level. This loss of hMLH1 protein occurred in the MSI-H invasive tumor but not in the adjacent carcinoma-in situ or dysplastic components that were MSS. The MSI-L and MSS forms of gastric carcinoma all showed predominantly unmethylated hMLHI promoter, positive hMLH1 protein and high hMLH1 mRNA level. On the other hand, hMSH2 protein was expressed in all of the tumors irrespective of the MSI status. Our results suggest that high-frequency MSI in sporadic gastric cancer is mostly due to epigenetic inactivation of hMLH1 in association with promoter methylation, and the loss of hMLH1 protein is a significant event in the development of invasive tumor.
Persistent Identifierhttp://hdl.handle.net/10722/49413
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorChu, KMen_HK
dc.contributor.authorChan, ASYen_HK
dc.contributor.authorHo, JCIen_HK
dc.date.accessioned2008-06-12T06:41:57Z-
dc.date.available2008-06-12T06:41:57Z-
dc.date.issued1999en_HK
dc.identifier.citationCancer Research, 1999, v. 59 n. 1, p. 159-164en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49413-
dc.description.abstractMutation of DNA mismatch repair genes has rarely been documented in sporadic gastric carcinoma with microsatellite instability (MSI). In sporadic colorectal carcinoma, hMLH1 promoter methylation associated with protein loss is found in the majority of high-frequency MSI eases. We investigated a series of 35 sporadic gastric carcinomas stratified into high-frequency MSI (MSI-H), low-frequency MSI (MSI-L) and microsatellite stable (MSS) groups and found that hypermethylation of the CpG island in the hMLH1 promoter region was present in 100% of MSI-H sporadic gastric carcinomas. In 90% of cases, there was an associated complete loss of hMLH1 protein, as detected by immunohistochemistry, and a markedly lowered hMLH1 mRNA level. This loss of hMLH1 protein occurred in the MSI-H invasive tumor but not in the adjacent carcinoma-in situ or dysplastic components that were MSS. The MSI-L and MSS forms of gastric carcinoma all showed predominantly unmethylated hMLHI promoter, positive hMLH1 protein and high hMLH1 mRNA level. On the other hand, hMSH2 protein was expressed in all of the tumors irrespective of the MSI status. Our results suggest that high-frequency MSI in sporadic gastric cancer is mostly due to epigenetic inactivation of hMLH1 in association with promoter methylation, and the loss of hMLH1 protein is a significant event in the development of invasive tumor.en_HK
dc.format.extent418 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCarcinoma - geneticsen_HK
dc.subject.meshDNA, Satellite - geneticsen_HK
dc.subject.meshMutationen_HK
dc.subject.meshNeoplasm Proteins - geneticsen_HK
dc.subject.meshStomach Neoplasms - geneticsen_HK
dc.titlehMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instabilityen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=59&issue=1&spage=159&epage=164&date=1999&atitle=hMLH1+promoter+methylation+and+lack+of+hMLH1+expression+in+sporadic+gastric+carcinomas+with+high-frequency+microsatellite+instabilityen_HK
dc.identifier.emailLeung, SY: suetyi@hku.hken_HK
dc.identifier.emailChung, LP: lpchung@hkucc.hku.hken_HK
dc.identifier.emailChu, KM: chukm@hkucc.hku.hken_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.identifier.authorityChung, LP=rp00249en_HK
dc.identifier.authorityChu, KM=rp00435en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid9892201-
dc.identifier.scopuseid_2-s2.0-0001119305en_HK
dc.identifier.hkuros39790-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0001119305&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume59en_HK
dc.identifier.issue1en_HK
dc.identifier.spage159en_HK
dc.identifier.epage164en_HK
dc.identifier.isiWOS:000077979300028-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK
dc.identifier.scopusauthoridYuen, ST=7103160927en_HK
dc.identifier.scopusauthoridChung, LP=24315879100en_HK
dc.identifier.scopusauthoridChu, KM=7402453538en_HK
dc.identifier.scopusauthoridChan, ASY=7403168075en_HK
dc.identifier.scopusauthoridHo, JCI=15029093800en_HK

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