Kuroki Tamotsu, Trapasso Francesco, Yendamuri Sai, Matsuyama Ayumi, Alder Hansjuerg, Mori Masaki, Croce Carlo M
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, Pennsylvania 19107, USA.
Clin Cancer Res. 2003 Apr;9(4):1441-5.
The RAS association domain family 1A (RASSF1A) gene, a candidate tumor suppressor gene, is frequently inactivated by hypermethylation of its promoter region in several human cancers. The aim of this study was to evaluate the promoter methylation status of the RASSF1A in esophageal squamous cell carcinoma.
We analyzed the methylation status of RASSF1A promoter by methylation-specific PCR in 23 esophageal squamous cell carcinoma cell lines and 48 primary tumors.
Hypermethylation of RASSF1A was found in 74% of cell lines and 52% of primary tumors. The presence of hypermethylation was statistically associated with loss of RASSF1A mRNA expression in both cell lines (P = 0.007) and primary tumors (P = 0.003). There was a statistically significant correlation between the presence of hypermethylation and tumor stage (P = 0.009).
Our findings suggest that epigenetic silencing of RASSF1A gene expression by promoter hypermethylation could play an important role in primary esophageal squamous cell carcinogenesis.
RAS关联结构域家族1A（RASSF1A）基因作为一种候选肿瘤抑制基因，在多种人类癌症中常因其启动子区域的高甲基化而失活。本研究旨在评估食管鳞状细胞癌中RASSF1A的启动子甲基化状态。
我们通过甲基化特异性PCR分析了23株食管鳞状细胞癌细胞系和48例原发性肿瘤中RASSF1A启动子的甲基化状态。
在74%的细胞系和52%的原发性肿瘤中发现了RASSF1A的高甲基化。在细胞系（P = 0.007）和原发性肿瘤（P = 0.003）中，高甲基化的存在与RASSF1A mRNA表达的缺失均具有统计学相关性。高甲基化的存在与肿瘤分期之间存在统计学显著相关性（P = 0.009）。
我们的研究结果表明，启动子高甲基化导致的RASSF1A基因表达的表观遗传沉默可能在原发性食管鳞状细胞癌发生中起重要作用。
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