Lee S H, Shin M S, Park W S, Kim S Y, Dong S M, Pi J H, Lee H K, Kim H S, Jang J J, Kim C S, Kim S H, Lee J Y, Yoo N J
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul.
Cancer Res. 1999 Jul 1;59(13):3068-72.
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 in cancer patients have been described solely in lymphoid-lineage malignancies. We analyzed somatic mutations and loss of heterozygosity of Fas gene in 43 transitional cell carcinomas of urinary bladder. Overall, 12 tumors (28%) were found to have Fas mutations, including 11 missense mutations and 1 frameshift mutation. Ten of the 12 mutations were located in the death domain known to be involved in the transduction of an apoptotic signal, and 8 of these 10 mutations showed an identical G to A transition at bp 993, indicating a potential hotspot in bladder cancers. Three of eight (38%) informative tumors carrying Fas mutations showed LOH at polymorphic sites in the promoter region. This is the first report on the Fas gene mutations in nonlymphoid malignancies, and our data suggest that alterations of the Fas gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some bladder cancers.
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内进行研究的，癌症患者中Fas的体细胞突变仅在淋巴系恶性肿瘤中有所描述。我们分析了43例膀胱移行细胞癌中Fas基因的体细胞突变和杂合性缺失情况。总体而言，发现12例肿瘤（28%）存在Fas突变，包括11例错义突变和1例移码突变。12例突变中有10例位于已知参与凋亡信号转导的死亡结构域，这10例突变中有8例在第993位碱基处出现相同的G到A转换，表明这可能是膀胱癌中的一个潜在热点。携带Fas突变的8例信息充分的肿瘤中有3例（38%）在启动子区域的多态性位点出现杂合性缺失。这是关于非淋巴系恶性肿瘤中Fas基因突变的首次报道，我们的数据表明Fas基因的改变可能导致其凋亡功能丧失，并有助于某些膀胱癌的发病机制。
