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Article: Genetic and Epigenetic Alterations of DLC-1 Gene in Hepatocellular Carcinoma

TitleGenetic and Epigenetic Alterations of DLC-1 Gene in Hepatocellular Carcinoma
Authors
Issue Date2003
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2003, v. 63 n. 22, p. 7646-7651 How to Cite?
AbstractHepatocellular carcinoma (HCC) is one of the most common fatal cancers in the world. However, the underlying molecular mechanisms contributing to hepatocarcinogenesis are still unclear. A putative tumor suppressor gene, namely DLC-1 (frequently deleted in liver cancer) was identified and mapped at chromosome 8p21.3-22, a recurrently deleted region in human cancers. The gene exerts inhibitory effects on the cell proliferation of HCC cells. In this study, we investigated the biological function, and genetic and epigenetic status of this gene in human HCC. With in vitro GTPase activating proteins activity assay, we established that DLC-1 protein was a GTPase-activating protein specific for RhoA and Cdc42. Deletion of the DLC-1 gene was frequent in human HCC, as revealed by loss of heterozygosity analysis performed on 100 human HCC cases with markers mapped at the DLC-1 locus, and allelic losses ranging from 44% to 50% of the informative cases. However, somatic mutations of the DLC-1 gene were rare. Moreover, with real-time quantitative PCR, we found that DLC-1 mRNA was significantly underexpressed in HCCs when compared with the corresponding nontumorous livers (P < 0.0001). In addition, the CpG island 5′ to the DLC-1 gene was methylated in 3 of 7 HCC cell lines and in 6 (24%) of 25 primary HCCs. These data suggest that transcriptional silencing by hypermethylation may contribute to the inactivation of the DLC-1 gene. Taken together, the results of our study suggest that both genetic and epigenetic alterations play an important role in inactivation of the DLC-1 gene in hepatocarcinogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/68003
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, CMen_HK
dc.contributor.authorLee, JMFen_HK
dc.contributor.authorChing, YPen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2010-09-06T06:00:24Z-
dc.date.available2010-09-06T06:00:24Z-
dc.date.issued2003en_HK
dc.identifier.citationCancer Research, 2003, v. 63 n. 22, p. 7646-7651en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68003-
dc.description.abstractHepatocellular carcinoma (HCC) is one of the most common fatal cancers in the world. However, the underlying molecular mechanisms contributing to hepatocarcinogenesis are still unclear. A putative tumor suppressor gene, namely DLC-1 (frequently deleted in liver cancer) was identified and mapped at chromosome 8p21.3-22, a recurrently deleted region in human cancers. The gene exerts inhibitory effects on the cell proliferation of HCC cells. In this study, we investigated the biological function, and genetic and epigenetic status of this gene in human HCC. With in vitro GTPase activating proteins activity assay, we established that DLC-1 protein was a GTPase-activating protein specific for RhoA and Cdc42. Deletion of the DLC-1 gene was frequent in human HCC, as revealed by loss of heterozygosity analysis performed on 100 human HCC cases with markers mapped at the DLC-1 locus, and allelic losses ranging from 44% to 50% of the informative cases. However, somatic mutations of the DLC-1 gene were rare. Moreover, with real-time quantitative PCR, we found that DLC-1 mRNA was significantly underexpressed in HCCs when compared with the corresponding nontumorous livers (P < 0.0001). In addition, the CpG island 5′ to the DLC-1 gene was methylated in 3 of 7 HCC cell lines and in 6 (24%) of 25 primary HCCs. These data suggest that transcriptional silencing by hypermethylation may contribute to the inactivation of the DLC-1 gene. Taken together, the results of our study suggest that both genetic and epigenetic alterations play an important role in inactivation of the DLC-1 gene in hepatocarcinogenesis.en_HK
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.subject.meshAzacitidine - analogs & derivatives - pharmacologyen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshCarcinoma, Hepatocellular - genetics - metabolismen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshCpG Islands - geneticsen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshGTPase-Activating Proteins - geneticsen_HK
dc.subject.meshGene Expression Regulation, Neoplasticen_HK
dc.subject.meshGene Silencingen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLiver Neoplasms - genetics - metabolismen_HK
dc.subject.meshLoss of Heterozygosityen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshRNA, Messenger - biosynthesis - geneticsen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.subject.meshTumor Suppressor Proteins - genetics - metabolismen_HK
dc.subject.meshcdc42 GTP-Binding Protein - metabolismen_HK
dc.subject.meshrac1 GTP-Binding Protein - metabolismen_HK
dc.subject.meshrhoA GTP-Binding Protein - metabolismen_HK
dc.titleGenetic and Epigenetic Alterations of DLC-1 Gene in Hepatocellular Carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=63&spage=7646&epage=7651&date=2003&atitle=Genetic+and+epigenetic+alterations+of+DLC-1+gene+in+hepatocellular+carcinomaen_HK
dc.identifier.emailWong, CM:jackwong@pathology.hku.hken_HK
dc.identifier.emailChing, YP:ypching@hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_HK
dc.identifier.authorityWong, CM=rp00231en_HK
dc.identifier.authorityChing, YP=rp00469en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid14633684-
dc.identifier.scopuseid_2-s2.0-0344844475en_HK
dc.identifier.hkuros86102en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0344844475&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume63en_HK
dc.identifier.issue22en_HK
dc.identifier.spage7646en_HK
dc.identifier.epage7651en_HK
dc.identifier.isiWOS:000186770700020-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWong, CM=16314668400en_HK
dc.identifier.scopusauthoridLee, JMF=36065603500en_HK
dc.identifier.scopusauthoridChing, YP=7005431277en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK

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