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Article: Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma

TitleAberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma
Authors
Keywords3p21
Methylation
Oesophageal carcinoma
RASSF1A
Tumor suppressor gene
Issue Date2006
PublisherSpandidos Publications. The Journal's web site is located at http://www.spandidos-publications.com/ijo/
Citation
International Journal Of Oncology, 2006, v. 28 n. 3, p. 767-773 How to Cite?
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.
DescriptionThe article can be viewed at http://www.spandidos-publications.com/ijo/28/3/767
Persistent Identifierhttp://hdl.handle.net/10722/67500
ISSN
2014 Impact Factor: 3.025
2013 SCImago Journal Rankings: 1.188
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, MLYen_HK
dc.contributor.authorTao, Qen_HK
dc.contributor.authorFu, LIen_HK
dc.contributor.authorWong, KYen_HK
dc.contributor.authorQiu, GHen_HK
dc.contributor.authorLaw, FBFen_HK
dc.contributor.authorTin, PCen_HK
dc.contributor.authorCheung, WLen_HK
dc.contributor.authorLee, PYen_HK
dc.contributor.authorTang, JCOen_HK
dc.contributor.authorTsao, GSWen_HK
dc.contributor.authorLam, KYen_HK
dc.contributor.authorLaw, Sen_HK
dc.contributor.authorWong, Jen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.date.accessioned2010-09-06T05:55:41Z-
dc.date.available2010-09-06T05:55:41Z-
dc.date.issued2006en_HK
dc.identifier.citationInternational Journal Of Oncology, 2006, v. 28 n. 3, p. 767-773en_HK
dc.identifier.issn1019-6439en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67500-
dc.descriptionThe article can be viewed at http://www.spandidos-publications.com/ijo/28/3/767-
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_HK
dc.languageengen_HK
dc.publisherSpandidos Publications. The Journal's web site is located at http://www.spandidos-publications.com/ijo/en_HK
dc.relation.ispartofInternational Journal of Oncologyen_HK
dc.subject3p21en_HK
dc.subjectMethylationen_HK
dc.subjectOesophageal carcinomaen_HK
dc.subjectRASSF1Aen_HK
dc.subjectTumor suppressor geneen_HK
dc.subject.meshCarcinoma, Squamous Cell - epidemiology - genetics - pathology-
dc.subject.meshDNA Methylation-
dc.subject.meshEsophageal Neoplasms - epidemiology - genetics - pathology-
dc.subject.meshPromoter Regions, Genetic - genetics-
dc.subject.meshTumor Suppressor Proteins - genetics-
dc.titleAberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1019-6439&volume=28&issue=3&spage=767&epage=773&date=2006&atitle=Aberrant+promoter+hypermethylation+and+silencing+of+the+critical+3p21+tumour+suppressor+gene,+RASSF1A,+in+Chinese+oesophageal+squamous+cell+carcinomaen_HK
dc.identifier.emailFu, LI: gracelfu@hku.hken_HK
dc.identifier.emailTsao, GSW: gswtsao@hku.hken_HK
dc.identifier.emailLaw, S: slaw@hku.hken_HK
dc.identifier.emailWong, J: jwong@hkucc.hku.hken_HK
dc.identifier.emailSrivastava, G: sgopesh@hkucc.hku.hken_HK
dc.identifier.authorityFu, LI=rp01435en_HK
dc.identifier.authorityTsao, GSW=rp00399en_HK
dc.identifier.authorityLaw, S=rp00437en_HK
dc.identifier.authorityWong, J=rp00322en_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid16465383-
dc.identifier.scopuseid_2-s2.0-33645237758en_HK
dc.identifier.hkuros115158en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33645237758&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume28en_HK
dc.identifier.issue3en_HK
dc.identifier.spage767en_HK
dc.identifier.epage773en_HK
dc.identifier.isiWOS:000235325000023-
dc.publisher.placeGreeceen_HK
dc.identifier.scopusauthoridWong, MLY=36683793500en_HK
dc.identifier.scopusauthoridTao, Q=7102578359en_HK
dc.identifier.scopusauthoridFu, LI=22979236700en_HK
dc.identifier.scopusauthoridWong, KY=55474654700en_HK
dc.identifier.scopusauthoridQiu, GH=7103292122en_HK
dc.identifier.scopusauthoridLaw, FBF=12792449100en_HK
dc.identifier.scopusauthoridTin, PC=6603931714en_HK
dc.identifier.scopusauthoridCheung, WL=7202743060en_HK
dc.identifier.scopusauthoridLee, PY=8731985700en_HK
dc.identifier.scopusauthoridTang, JCO=14056850300en_HK
dc.identifier.scopusauthoridTsao, GSW=7102813116en_HK
dc.identifier.scopusauthoridLam, KY=7403657165en_HK
dc.identifier.scopusauthoridLaw, S=7202241293en_HK
dc.identifier.scopusauthoridWong, J=8049324500en_HK
dc.identifier.scopusauthoridSrivastava, G=7202242238en_HK

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