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

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Title Aberrant promoter hypermethylation and silencing of the critical 3p21 tumor suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma
Author Wong, Michelle Ly; Tao, Qian; Fu, Li; Wong, Kai-Yau; Qiu, Guo-Hua; Law, Fian B. F.; Tin, Pui-Chi; Chenug, Wai-Ling; Lee, Pin-Yin; Tang, Jonny Cheuk-On; Tsao, George S. W.; Lam, Alfred; Law, Simon; Wong, John; Srivastava, Gopesh
Journal Name International Journal of Oncology
Editor Professor D.A. Spandidos
Year Published 2006
Place of publication Greece
Publisher Demetrios A. Spandidos
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.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.spandidos.com/ijo/
Copyright Statement Copyright 2006 Spandidos Publications. The attached file is reproduced here in accordance with the copyright policy of the publisher.
Volume 28
Page from 767
Page to 773
ISSN 1019-6439
Date Accessioned 2007-03-12
Language en_AU
Research Centre Molecular Basis of Disease; Menzies Health Institute Qld
Faculty Griffith Health Faculty
Subject Pathology
URI http://hdl.handle.net/10072/14121
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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