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Article: DLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG methylation in colon and gastric cancers

TitleDLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG methylation in colon and gastric cancers
Authors
KeywordsCpG island
Tumour suppressor gene (TSG)
Methylation
DLEC1
Colon and gastric cancers
Issue Date2009
Citation
British Journal of Cancer, 2009, v. 100, n. 4, p. 663-669 How to Cite?
AbstractPromoter CpG methylation of tumour suppressor genes (TSGs) is an epigenetic biomarker for TSG identification and molecular diagnosis. We screened genome wide for novel methylated genes through methylation subtraction of a genetic demethylation model of colon cancer (double knockout of DNMT1 and DNMT3B in HCT116) and identified DLEC1 (Deleted in lung and oesophageal cancer 1), a major 3p22.3 TSG, as one of the methylated targets. We further found that DLEC1 was downregulated or silenced in most colorectal and gastric cell lines due to promoter methylation, whereas broadly expressed in normal tissues including colon and stomach, and unmethylated in expressing cell lines and immortalised normal colon epithelial cells. DLEC1 expression was reactivated through pharmacologic or genetic demethylation, indicating a DNMT1/DNMT3B-mediated methylation silencing. Aberrant methylation was further detected in primary colorectal (10 out of 34, 29%) and gastric tumours (30 out of 89, 34%), but seldom in paired normal colon (0 out of 17) and gastric (1 out of 20, 5%) samples. No correlation between DLEC1 methylation and clinical parameters of gastric cancers was found. Ectopic expression of DLEC1 in silenced HCT116 and MKN45 cells strongly inhibited their clonogenicity. Thus, DLEC1 is a functional tumour suppressor, being frequently silenced by epigenetic mechanism in gastrointestinal tumours. © 2009 Cancer Research UK.
Persistent Identifierhttp://hdl.handle.net/10722/207022
ISSN
2015 Impact Factor: 5.569
2015 SCImago Journal Rankings: 2.939

 

DC FieldValueLanguage
dc.contributor.authorYing, Jianming-
dc.contributor.authorPoon, FanFong-
dc.contributor.authorYu, Jun-
dc.contributor.authorGeng, Hua-
dc.contributor.authorWong, Ada Ho Yan-
dc.contributor.authorQiu, Guohua-
dc.contributor.authorGoh, HweeKoon-
dc.contributor.authorRha, Sunyoung-
dc.contributor.authorTian, Linwei-
dc.contributor.authorChan, Anthony-
dc.contributor.authorSung, Joseph-
dc.contributor.authorTao, Qian-
dc.date.accessioned2014-12-09T04:31:15Z-
dc.date.available2014-12-09T04:31:15Z-
dc.date.issued2009-
dc.identifier.citationBritish Journal of Cancer, 2009, v. 100, n. 4, p. 663-669-
dc.identifier.issn0007-0920-
dc.identifier.urihttp://hdl.handle.net/10722/207022-
dc.description.abstractPromoter CpG methylation of tumour suppressor genes (TSGs) is an epigenetic biomarker for TSG identification and molecular diagnosis. We screened genome wide for novel methylated genes through methylation subtraction of a genetic demethylation model of colon cancer (double knockout of DNMT1 and DNMT3B in HCT116) and identified DLEC1 (Deleted in lung and oesophageal cancer 1), a major 3p22.3 TSG, as one of the methylated targets. We further found that DLEC1 was downregulated or silenced in most colorectal and gastric cell lines due to promoter methylation, whereas broadly expressed in normal tissues including colon and stomach, and unmethylated in expressing cell lines and immortalised normal colon epithelial cells. DLEC1 expression was reactivated through pharmacologic or genetic demethylation, indicating a DNMT1/DNMT3B-mediated methylation silencing. Aberrant methylation was further detected in primary colorectal (10 out of 34, 29%) and gastric tumours (30 out of 89, 34%), but seldom in paired normal colon (0 out of 17) and gastric (1 out of 20, 5%) samples. No correlation between DLEC1 methylation and clinical parameters of gastric cancers was found. Ectopic expression of DLEC1 in silenced HCT116 and MKN45 cells strongly inhibited their clonogenicity. Thus, DLEC1 is a functional tumour suppressor, being frequently silenced by epigenetic mechanism in gastrointestinal tumours. © 2009 Cancer Research UK.-
dc.languageeng-
dc.relation.ispartofBritish Journal of Cancer-
dc.subjectCpG island-
dc.subjectTumour suppressor gene (TSG)-
dc.subjectMethylation-
dc.subjectDLEC1-
dc.subjectColon and gastric cancers-
dc.titleDLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG methylation in colon and gastric cancers-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.bjc.6604888-
dc.identifier.pmid19156137-
dc.identifier.scopuseid_2-s2.0-60349109571-
dc.identifier.volume100-
dc.identifier.issue4-
dc.identifier.spage663-
dc.identifier.epage669-
dc.identifier.eissn1532-1827-

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