The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas
The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas
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DOI：
10.1038/sj.onc.1204469
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发表时间：
2001-06-14
期刊：
影响因子：
8
通讯作者：
Pfeifer, GP
中科院分区：
文献类型：
--
作者：
Dammann, R;Takahashi, T;Pfeifer, GP
超过 90% 的小细胞肺癌 (SCLC) 均发生 3p21.3 杂合性丢失。从肺肿瘤抑制基因座 3p21.3 克隆的 Ras 关联域家族 1 (RASSF1) 基因由两个主要的替代转录物 RASSF1A 和 RASSF1C 组成。在 40% 的原发性非小细胞肺癌和几种肿瘤细胞系中观察到同种型 A (RASSF1A) 的表观遗传失活。转染RASSF1A可抑制体外和裸鼠体内肺癌细胞的生长。在这里，我们分析了原发性 SCLC 中 RASSF1A 和 RASSF1C 的 CPG 岛启动子的甲基化状态。在 28 个 SCLC 中的 22 个 (= 79%) 中，RASSF1A 的启动子在分析的所有 CpG 位点处均高度甲基化，没有一个 SCLC 显示出 RASSF1C 的 CpG 岛甲基化的证据。结果表明 RASSF1A 基因 CpG 岛启动子的高甲基化与 SCLC 发病机制相关。
Loss of heterozygosity at 3p21.3 occurs in more than 90% of small cell lung carcinomas (SCLCs). The Ras association domain family 1 (RASSF1) gene cloned from the lung tumor suppressor locus 3p21.3 consists of two major alternative transcripts, RASSF1A and RASSF1C. Epigenetic inactivation of isoform A (RASSF1A) was observed in 40% of primary non-small cell lung carcinomas and in several tumor cell lines. Transfection of RASSF1A suppressed the growth of lung cancer cells in vitro and in nude mice. Here we have analysed the methylation status of the CPG island promoters of RASSF1A and RASSF1C in primary SCLCs. In 22 of 28 SCLCs (=79%) the promoter of RASSF1A was highly methylated at all CpG sites analysed, None of the SCLCs showed evidence for methylation of the CpG island of RASSF1C. The results suggest that hypermethylation of the CpG island promoter of the RASSF1A gene is associated with SCLC pathogenesis.