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dc.contributor.authorWong, Michelleen_US
dc.contributor.authorTao, Qianen_US
dc.contributor.authorFu, Lien_US
dc.contributor.authorWong, Kai-Yauen_US
dc.contributor.authorQiu, Guo-Huaen_US
dc.contributor.authorB. F. Law, Fianen_US
dc.contributor.authorTin, Pui-Chien_US
dc.contributor.authorChenug, Wai-Lingen_US
dc.contributor.authorLee, Pin-Yinen_US
dc.contributor.authorTang, Jonny Cheuk-Onen_US
dc.contributor.authorS. W. Tsao, Georgeen_US
dc.contributor.authorLam, Alfreden_US
dc.contributor.authorLaw, Simonen_US
dc.contributor.authorWong, Johnen_US
dc.contributor.authorSrivastava, Gopeshen_US
dc.contributor.editorProfessor D.A. Spandidosen_US
dc.date.accessioned2017-04-24T11:54:26Z
dc.date.available2017-04-24T11:54:26Z
dc.date.issued2006en_US
dc.date.modified2008-02-05T06:25:58Z
dc.identifier.issn10196439en_US
dc.identifier.urihttp://hdl.handle.net/10072/14121
dc.description.abstract3p21 is an important locus harbouring critical tumour suppressor genes (TSG), which are implicated in the pathogenesis of multiple tumours, including oesophageal carcinoma. RASSF1A is a 3p21.3 candidate TSG frequently inactivated by promoter methylation in multiple tumours. We investigated RASSF1A promoter methylation and gene expression in Chinese oesophageal squamous cell carcinoma (ESCC) to compare it to data from Japanese patients. Methylation-specific PCR (MSP) showed that RASSF1A was partially methylated in 3/7 (43%) cell lines; 22/64 (34%) primary tumours and 3/64 (5%) corresponding non-tumour samples; and was not methylated in 2 immortalized normal oesophageal epithelial cell lines and 6 normal oesophageal epithelium samples. Bisulfite genome sequencing confirmed the MSP results. Promoter hypermethylation correlated well with RASSF1A mRNA down-regulation. Treatment of cell lines with 5-aza-2'-deoxycytidine activated RASSF1A mRNA expression along with promoter demethylation. RASSF1A hypermethylation in the Chinese cohort was much lower than in a published report of Japanese ESCC patients (52%) and cell lines (74%). Our own analysis of Japanese ESCC cell lines for direct comparison also detected a high frequency of RASSF1A hypermethylation (8/10; 80%) and high levels of hypermethylation at each CpG site. No significant association between RASSF1A hypermethylation and histological differentiation (p=0.953), tumour staging (p=0.117), or survival (p=0.7571) was found in Chinese ESCC, unlike the results of Japanese patients. The incidence of oesophageal cancer shows marked variation by geographic area and ethnic group; it is almost three times higher in China than in Japan, indicating possible different pathogenetic mechanisms. Our results show that RASSF1A hypermethylation in ESCC has epidemiological/ethnic differences, and suggest that Chinese ESCC may result from different pathogenetic mechanisms.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.format.extent218531 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherDemetrios A. Spandidosen_US
dc.publisher.placeGreeceen_US
dc.publisher.urihttp://www.spandidos.com/ijo/en_AU
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom767en_US
dc.relation.ispartofpageto773en_US
dc.relation.ispartofjournalInternational Journal of Oncologyen_US
dc.relation.ispartofvolume28en_US
dc.rights.retentionNen_AU
dc.subject.fieldofresearchcode321020en_US
dc.titleAberrant promoter hypermethylation and silencing of the critical 3p21 tumor suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinomaen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightCopyright 2006 Spandidos Publications. The attached file is reproduced here in accordance with the copyright policy of the publisher.en_AU
gro.date.issued2006
gro.hasfulltextFull Text


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