Shin M S, Park W S, Kim S Y, Kim H S, Kang S J, Song K Y, Park J Y, Dong S M, Pi J H, Oh R R, Lee J Y, Yoo N J, Lee S H
Departments of Pathology, Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Am J Pathol. 1999 Jun;154(6):1785-91. doi: 10.1016/S0002-9440(10)65434-X.
Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling. The key role of the Fas system in negative growth regulation has been studied mostly within the immune system, and somatic mutations of Fas gene in cancer patients have been described solely in lymphoid-lineage malignancies. However, many nonlymphoid tumor cells have been found to be resistant to Fas-mediated apoptosis, which suggests that Fas mutations, one of the possible mechanisms for Fas resistance, may be involved in the pathogenesis of nonlymphoid malignancies as well. In this study, we have analyzed the entire coding region and all splice sites of the Fas gene for the detection of the gene mutations in 44 human malignant melanomas in skin by polymerase chain reaction, single-strand conformation polymorphism, and DNA sequencing. Overall, 3 tumors (6.8%) were found to have the Fas mutations, which were all missense variants and identified in the cytoplasmic region (death domain) known to be involved in the transduction of an apoptotic signal. The data presented here suggest that somatic alterations of the Fas gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human malignant melanomas.
Fas（Apo-1/CD95）是一种参与细胞死亡信号传导的细胞表面受体。Fas系统在负性生长调节中的关键作用主要是在免疫系统中进行研究的，并且癌症患者中Fas基因的体细胞突变仅在淋巴系恶性肿瘤中被描述。然而，已发现许多非淋巴样肿瘤细胞对Fas介导的凋亡具有抗性，这表明Fas突变作为Fas抗性的可能机制之一，也可能参与非淋巴样恶性肿瘤的发病机制。在本研究中，我们通过聚合酶链反应、单链构象多态性和DNA测序分析了44例人类皮肤恶性黑色素瘤中Fas基因的整个编码区和所有剪接位点，以检测基因突变。总体而言，发现3个肿瘤（6.8%）存在Fas突变，这些突变均为错义变体，且在已知参与凋亡信号转导的胞质区域（死亡结构域）中被鉴定出来。此处呈现的数据表明，Fas基因的体细胞改变可能导致其凋亡功能丧失，并有助于某些人类恶性黑色素瘤的发病机制。
