Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/33575
Title: Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma
Authors: Wong, MLY
Tao, Q
Fu, LI
Wong, KY
Qiu, GH
Law, FBF
Tin, PC
Cheung, WL
Lee, PY
Tang, JCO 
Tsao, GSW
Lam, KY
Law, S
Wong, J
Srivastava, G
Keywords: 3p21
Methylation
Oesophageal carcinoma
RASSF1A
Tumor suppressor gene
Issue Date: 2006
Publisher: Spandidos Publications
Source: International journal of oncology, 2006, v. 28, no. 3, p. 767-773 How to cite?
Journal: International journal of oncology 
Abstract: 3p21 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.
URI: http://hdl.handle.net/10397/33575
ISSN: 1019-6439
EISSN: 1791-2423
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