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Article: Promoter hypermethylation of tumor-related genes in the progression of colorectal neoplasia

TitlePromoter hypermethylation of tumor-related genes in the progression of colorectal neoplasia
Authors
Issue Date2004
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2004, v. 112 n. 5, p. 846-853 How to Cite?
AbstractGene promoter hypermethylation is increasingly recognized to play an important role in cancer development through silencing of gene transcription. This study determined the methylation profiles of primary colorectal cancers and adenomas to elucidate the role of epigenetic changes in different stages of colorectal carcinogenesis. We examined the methylation profiles of 47 sporadic colorectal cancers, 36 colonic adenomas from patients without cancer and 34 colonic biopsies from patients without colonic lesions. Paired adjacent dysplasia tissues obtained from 17 cancer patients were also examined. Promoter hypermethylation in 10 tumor-related genes (APC, ATM, GSTPI, HLTF, MGMT, hMLH1, p14, p15, SOCS-1 and TIMP-3) were studied by methylation-specific PCR. Promoter hypermethylation was frequently detected in more than 40% of colonic cancers and adenomas in APC, ATM, HLTF, MGMT and hMLH1 genes (p < 0.0001 vs. normal). While low level of methylation was detected in p14, p15 and TIMP-3, there was no methylation detected in GSTPI and SOCS-1. The frequencies of methylation were comparable between tumors and adenomas, and advanced and non-advanced adenoma. In contrast, K-ras mutation was only detected in advanced adenomas and cancers. Concurrent methylation in ≥ 3 genes was found in 66.7% adenomas and 68.1% cancers but not in normal colonic tissues. Methylation was associated with reduced protein expressions in colorectal adenomas and cancers. Moreover, methylation in ATM was more common in older cancer patients (p = 0.002), but there was no significant association between promoter hypermethylation and other clinicopathologic characteristics of cancer. Our study demonstrated the early and specific involvement of promoter hypermethylation in the colorectal adenoma-carcinoma sequence. © 2004 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/163280
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorBai, AHCen_US
dc.contributor.authorTong, JHMen_US
dc.contributor.authorTo, KFen_US
dc.contributor.authorChan, MWYen_US
dc.contributor.authorMan, EPSen_US
dc.contributor.authorLo, KWen_US
dc.contributor.authorLee, JFYen_US
dc.contributor.authorSung, JJYen_US
dc.contributor.authorLeung, WKen_US
dc.date.accessioned2012-09-05T05:29:35Z-
dc.date.available2012-09-05T05:29:35Z-
dc.date.issued2004en_US
dc.identifier.citationInternational Journal Of Cancer, 2004, v. 112 n. 5, p. 846-853en_US
dc.identifier.issn0020-7136en_US
dc.identifier.urihttp://hdl.handle.net/10722/163280-
dc.description.abstractGene promoter hypermethylation is increasingly recognized to play an important role in cancer development through silencing of gene transcription. This study determined the methylation profiles of primary colorectal cancers and adenomas to elucidate the role of epigenetic changes in different stages of colorectal carcinogenesis. We examined the methylation profiles of 47 sporadic colorectal cancers, 36 colonic adenomas from patients without cancer and 34 colonic biopsies from patients without colonic lesions. Paired adjacent dysplasia tissues obtained from 17 cancer patients were also examined. Promoter hypermethylation in 10 tumor-related genes (APC, ATM, GSTPI, HLTF, MGMT, hMLH1, p14, p15, SOCS-1 and TIMP-3) were studied by methylation-specific PCR. Promoter hypermethylation was frequently detected in more than 40% of colonic cancers and adenomas in APC, ATM, HLTF, MGMT and hMLH1 genes (p < 0.0001 vs. normal). While low level of methylation was detected in p14, p15 and TIMP-3, there was no methylation detected in GSTPI and SOCS-1. The frequencies of methylation were comparable between tumors and adenomas, and advanced and non-advanced adenoma. In contrast, K-ras mutation was only detected in advanced adenomas and cancers. Concurrent methylation in ≥ 3 genes was found in 66.7% adenomas and 68.1% cancers but not in normal colonic tissues. Methylation was associated with reduced protein expressions in colorectal adenomas and cancers. Moreover, methylation in ATM was more common in older cancer patients (p = 0.002), but there was no significant association between promoter hypermethylation and other clinicopathologic characteristics of cancer. Our study demonstrated the early and specific involvement of promoter hypermethylation in the colorectal adenoma-carcinoma sequence. © 2004 Wiley-Liss, Inc.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_US
dc.relation.ispartofInternational Journal of Canceren_US
dc.subject.meshAdenoma - Genetics - Pathologyen_US
dc.subject.meshBiopsyen_US
dc.subject.meshCarcinoma - Genetics - Pathologyen_US
dc.subject.meshCase-Control Studiesen_US
dc.subject.meshCell Transformation, Neoplasticen_US
dc.subject.meshColorectal Neoplasms - Genetics - Pathologyen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshDisease Progressionen_US
dc.subject.meshGene Silencingen_US
dc.subject.meshHumansen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshTranscription, Geneticen_US
dc.titlePromoter hypermethylation of tumor-related genes in the progression of colorectal neoplasiaen_US
dc.typeArticleen_US
dc.identifier.emailLeung, WK:waikleung@hku.hken_US
dc.identifier.authorityLeung, WK=rp01479en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/ijc.20485en_US
dc.identifier.pmid15386372-
dc.identifier.scopuseid_2-s2.0-7044232415en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-7044232415&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume112en_US
dc.identifier.issue5en_US
dc.identifier.spage846en_US
dc.identifier.epage853en_US
dc.identifier.isiWOS:000224824800016-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridBai, AHC=7006523130en_US
dc.identifier.scopusauthoridTong, JHM=7202724564en_US
dc.identifier.scopusauthoridTo, KF=7101911940en_US
dc.identifier.scopusauthoridChan, MWY=7402597788en_US
dc.identifier.scopusauthoridMan, EPS=7004439159en_US
dc.identifier.scopusauthoridLo, KW=7402101603en_US
dc.identifier.scopusauthoridLee, JFY=36063182100en_US
dc.identifier.scopusauthoridSung, JJY=35405352400en_US
dc.identifier.scopusauthoridLeung, WK=7201504523en_US

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