Alterations of Fas (APO-1/CD95) gene in transitional cell carcinomas of urinary bladder.
Alterations of Fas (APO-1/CD95) gene in transitional cell carcinomas of urinary bladder.
复制标题
膀胱移行细胞癌中 Fas (APO-1/CD95) 基因的改变。
作者：
S. Lee;M. Shin;W. Park;S. Y. Kim;Seung Myung Dong;J. Pi;H. Lee;Ho;Ja;C. Kim;S. H. Kim;Jung Young Lee;N. Yoo
Fas（Apo-1/CD 95）是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在免疫系统中进行研究，并且癌症患者中Fas的体细胞突变仅在淋巴系恶性肿瘤中描述。我们分析了43例膀胱移行细胞癌Fas基因的体细胞突变和杂合性丢失。总的来说，12个肿瘤（28%）被发现有Fas突变，包括11个错义突变和1个移码突变。12个突变中的10个位于已知参与凋亡信号转导的死亡结构域中，并且这10个突变中的8个在bp 993处显示出相同的G到A转变，表明膀胱癌中的潜在热点。8例携带Fas突变的信息性肿瘤中有3例（38%）在启动子区的多态性位点显示洛缺失。这是第一个报告Fas基因突变的非淋巴恶性肿瘤，我们的数据表明，Fas基因的改变可能会导致其凋亡功能的丧失，并有助于一些膀胱癌的发病机制。
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.
影响因子：
158.5
作者：
Drappa, J;Vaishnaw, AK;Elkon, KB
通讯作者：
Elkon, KB