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Article: Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma
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TitleAberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma
 
AuthorsWong, MLY6
Tao, Q5 6 2
Fu, LI2
Wong, KY6
Qiu, GH2
Law, FBF6
Tin, PC6
Cheung, WL6
Lee, PY1
Tang, JCO6 3 4
Tsao, GSW1
Lam, KY1
Law, S1
Wong, J1
Srivastava, G6
 
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/
 
CitationInternational 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
 
ISSN1019-6439
2013 Impact Factor: 2.773
2013 SCImago Journal Rankings: 1.188
 
ISI Accession Number IDWOS:000235325000023
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorWong, MLY
 
dc.contributor.authorTao, Q
 
dc.contributor.authorFu, LI
 
dc.contributor.authorWong, KY
 
dc.contributor.authorQiu, GH
 
dc.contributor.authorLaw, FBF
 
dc.contributor.authorTin, PC
 
dc.contributor.authorCheung, WL
 
dc.contributor.authorLee, PY
 
dc.contributor.authorTang, JCO
 
dc.contributor.authorTsao, GSW
 
dc.contributor.authorLam, KY
 
dc.contributor.authorLaw, S
 
dc.contributor.authorWong, J
 
dc.contributor.authorSrivastava, G
 
dc.date.accessioned2010-09-06T05:55:41Z
 
dc.date.available2010-09-06T05:55:41Z
 
dc.date.issued2006
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.descriptionThe article can be viewed at http://www.spandidos-publications.com/ijo/28/3/767
 
dc.identifier.citationInternational Journal Of Oncology, 2006, v. 28 n. 3, p. 767-773 [How to Cite?]
 
dc.identifier.epage773
 
dc.identifier.hkuros115158
 
dc.identifier.isiWOS:000235325000023
 
dc.identifier.issn1019-6439
2013 Impact Factor: 2.773
2013 SCImago Journal Rankings: 1.188
 
dc.identifier.issue3
 
dc.identifier.openurl
 
dc.identifier.pmid16465383
 
dc.identifier.scopuseid_2-s2.0-33645237758
 
dc.identifier.spage767
 
dc.identifier.urihttp://hdl.handle.net/10722/67500
 
dc.identifier.volume28
 
dc.languageeng
 
dc.publisherSpandidos Publications. The Journal's web site is located at http://www.spandidos-publications.com/ijo/
 
dc.publisher.placeGreece
 
dc.relation.ispartofInternational Journal of Oncology
 
dc.relation.referencesReferences in Scopus
 
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.subject3p21
 
dc.subjectMethylation
 
dc.subjectOesophageal carcinoma
 
dc.subjectRASSF1A
 
dc.subjectTumor suppressor gene
 
dc.titleAberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Johns Hopkins Singapore
  3. Hong Kong Polytechnic University
  4. Griffith University
  5. The Johns Hopkins School of Medicine
  6. Chinese University of Hong Kong