Pfeifer G P, Dammann R
Department of Biology, Beckman Research Institute, City of Hope Cancer Center, Duarte, CA 91010, USA.
Biochemistry (Mosc). 2005 May;70(5):576-83. doi: 10.1007/s10541-005-0151-y.
Loss of heterozygosity of a segment at 3p21.3 is frequently observed in lung cancer and several other carcinomas. We have identified the Ras-association domain family 1A gene (RASSF1A), which is localized at 3p21.3 in a minimum deletion sequence. De novo methylation of the RASSF1A promoter is one of the most frequent epigenetic inactivation events detected in human cancer and leads to silencing of RASSF1A expression. Hypermethylation of RASSF1A was frequently found in most major types of human tumors including lung, breast, prostate, pancreas, kidney, liver, cervical, thyroid and many other cancers. The detection of RASSF1A methylation in body fluids such as serum, urine, and sputum promises to be a useful marker for early cancer detection. The functional analysis of RASSF1A reveals a potential involvement of this protein in apoptotic signaling, microtubule stabilization, and cell cycle progression.
在肺癌和其他几种癌症中经常观察到3p21.3区域的杂合性缺失。我们已经鉴定出Ras关联结构域家族1A基因（RASSF1A），其位于3p21.3的最小缺失序列中。RASSF1A启动子的从头甲基化是在人类癌症中检测到的最常见的表观遗传失活事件之一，并导致RASSF1A表达沉默。RASSF1A的高甲基化在大多数主要类型的人类肿瘤中经常被发现，包括肺癌、乳腺癌、前列腺癌、胰腺癌、肾癌、肝癌、宫颈癌、甲状腺癌和许多其他癌症。在血清、尿液和痰液等体液中检测RASSF1A甲基化有望成为早期癌症检测的有用标志物。RASSF1A的功能分析揭示了该蛋白可能参与凋亡信号传导、微管稳定和细胞周期进程。
