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Article: Hypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesis

TitleHypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesis
Authors
KeywordsBLU
DNA hypermethylation
DNMT1
Endometrial cancer
hDAB2IP
RASSF1A
RASSF2A
Issue Date2008
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, 2008, v. 123 n. 2, p. 296-302 How to Cite?
AbstractEpigenetic aberration is known to be important in human carcinogenesis. Promoter methylation status of RAS effector related genes, RASSF1A, RASSF2A, hDAB2IP (m2a and m2b regions) and BLU, was evaluated in 76 endometrial carcinomas and their non-neoplastic endometrial tissue by methylation specific PCR. Hypermethylation of at least one of the 5 genes was detected in 73.7% of carcinomas. There were significant correlations between methylation of hDAB2IP and RASSF1A, RASSF2A (p = 0.042, p = 0.012, respectively). Significantly, more frequent RASSF1A hypermethylation was found in Type I endometrioid carcinomas than Type II carcinomas (p = 0.049). Among endometrioid cancers, significant association between RASSF1A hypermethylation and advanced stage, as well as between methylation of hDAB2IP at m2a region with deep myometrial invasion (p < 0.05) was observed. mRNA expression of RASSF1, RASSF2A and BLU in endometrial cancer cell lines significantly increased after treatment with the demethylating agent 5-Aza-2′-deoxycytidine supporting the repressive effect of hypermethylation on their transcription. Immunohistochemical study of DNMT1 on eight normal endometrium, 16 hyperplastic endometrium without atypia, 40 atypical complex hyperplasia and 79 endometrial carcinomas showed progressive increase in DNMT1 immunoreactivity from normal endometrium to endometrial hyperplasia and endometrioid carcinomas (p = 0.001). Among carcinomas, distinctly higher DNMT1 expression was observed in Type I endometrioid carcinomas (p < 0.001). DNMT1 immunoreactivity correlated with RASSF1A and RASSF2A methylation (p < 0.05). The data suggested that hypermethylation of RAS related genes, particularly RASSF1A, was involved in endometrial carcinogenesis with possible divergent patterns in different histological types. DNMT1 protein overexpression might contribute to such aberrant DNA hypermethylation of specific tumor suppressor genes in endometrial cancers. © 2008 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/60392
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiao, Xen_HK
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorChan, KYKen_HK
dc.contributor.authorWong, ESYen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorChan, QKYen_HK
dc.contributor.authorLi, ASMen_HK
dc.contributor.authorKhoo, USen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2010-05-31T04:09:43Z-
dc.date.available2010-05-31T04:09:43Z-
dc.date.issued2008en_HK
dc.identifier.citationInternational Journal Of Cancer, 2008, v. 123 n. 2, p. 296-302en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/60392-
dc.description.abstractEpigenetic aberration is known to be important in human carcinogenesis. Promoter methylation status of RAS effector related genes, RASSF1A, RASSF2A, hDAB2IP (m2a and m2b regions) and BLU, was evaluated in 76 endometrial carcinomas and their non-neoplastic endometrial tissue by methylation specific PCR. Hypermethylation of at least one of the 5 genes was detected in 73.7% of carcinomas. There were significant correlations between methylation of hDAB2IP and RASSF1A, RASSF2A (p = 0.042, p = 0.012, respectively). Significantly, more frequent RASSF1A hypermethylation was found in Type I endometrioid carcinomas than Type II carcinomas (p = 0.049). Among endometrioid cancers, significant association between RASSF1A hypermethylation and advanced stage, as well as between methylation of hDAB2IP at m2a region with deep myometrial invasion (p < 0.05) was observed. mRNA expression of RASSF1, RASSF2A and BLU in endometrial cancer cell lines significantly increased after treatment with the demethylating agent 5-Aza-2′-deoxycytidine supporting the repressive effect of hypermethylation on their transcription. Immunohistochemical study of DNMT1 on eight normal endometrium, 16 hyperplastic endometrium without atypia, 40 atypical complex hyperplasia and 79 endometrial carcinomas showed progressive increase in DNMT1 immunoreactivity from normal endometrium to endometrial hyperplasia and endometrioid carcinomas (p = 0.001). Among carcinomas, distinctly higher DNMT1 expression was observed in Type I endometrioid carcinomas (p < 0.001). DNMT1 immunoreactivity correlated with RASSF1A and RASSF2A methylation (p < 0.05). The data suggested that hypermethylation of RAS related genes, particularly RASSF1A, was involved in endometrial carcinogenesis with possible divergent patterns in different histological types. DNMT1 protein overexpression might contribute to such aberrant DNA hypermethylation of specific tumor suppressor genes in endometrial cancers. © 2008 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.en_HK
dc.subjectBLUen_HK
dc.subjectDNA hypermethylationen_HK
dc.subjectDNMT1en_HK
dc.subjectEndometrial canceren_HK
dc.subjecthDAB2IPen_HK
dc.subjectRASSF1Aen_HK
dc.subjectRASSF2Aen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshCarcinoma, Endometrioid - enzymology - genetics - metabolism - pathologyen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshDNA Primersen_HK
dc.subject.meshEndometrial Neoplasms - enzymology - genetics - metabolism - pathologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Expression Regulation, Enzymologicen_HK
dc.subject.meshGene Expression Regulation, Neoplasticen_HK
dc.subject.meshGenes, Tumor Suppressoren_HK
dc.subject.meshGenes, rasen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshPolymerase Chain Reactionen_HK
dc.subject.meshProteins - metabolismen_HK
dc.subject.meshRNA, Messenger - metabolismen_HK
dc.subject.meshRepressor Proteins - metabolismen_HK
dc.subject.meshTumor Suppressor Proteins - metabolismen_HK
dc.subject.meshras GTPase-Activating Proteins - metabolismen_HK
dc.titleHypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=123&issue=2&spage=296&epage=302&date=2008&atitle=Hypermethylation+of+RAS+effector+related+genes+and+DNA+methyltransferase+1+expression+in+endometrial+carcinogenesisen_HK
dc.identifier.emailSiu, MKY: mkysiu@hkucc.hku.hken_HK
dc.identifier.emailChan, KYK: kelvinc@pathology.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailKhoo, US: uskhoo@hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.authoritySiu, MKY=rp00275en_HK
dc.identifier.authorityChan, KYK=rp00453en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityKhoo, US=rp00362en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.23494en_HK
dc.identifier.pmid18404674en_HK
dc.identifier.scopuseid_2-s2.0-44949106316en_HK
dc.identifier.hkuros145273en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-44949106316&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume123en_HK
dc.identifier.issue2en_HK
dc.identifier.spage296en_HK
dc.identifier.epage302en_HK
dc.identifier.isiWOS:000256760300008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLiao, X=7202134156en_HK
dc.identifier.scopusauthoridSiu, MKY=24924018400en_HK
dc.identifier.scopusauthoridChan, KYK=7406034195en_HK
dc.identifier.scopusauthoridWong, ESY=23101622300en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridChan, QKY=8390404100en_HK
dc.identifier.scopusauthoridLi, ASM=24076332400en_HK
dc.identifier.scopusauthoridKhoo, US=7004195799en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK

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