Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma
Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma
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DOI：
10.1038/sj.onc.1204103
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发表时间：
2001-01-18
期刊：
影响因子：
8
通讯作者：
Yoo, NJ
中科院分区：
文献类型：
--
作者：
Lee, SH;Shin, MS;Yoo, NJ
肿瘤坏死因子相关凋亡诱导配体-受体1（TRAIL-R1）和肿瘤坏死因子相关凋亡诱导配体-受体2（TRAIL-R2）是参与肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导的细胞死亡信号传导的细胞表面受体。TRAIL-R1和TRAIL-R2基因最近被定位于染色体8 p21 -22，这是包括非霍奇金淋巴瘤（NHL）在内的许多类型的人类肿瘤中等位基因缺失的常见位点。我们推测TRAIL-R1和TRAIL-R2的突变可能参与NHL的发生，并且这些突变可能是导致8 p21 - 10 p21等位基因丢失的原因。本研究应用聚合酶链反应（PCR）单链构象多态性（SSCP）技术，对117例NHL患者的TRAIL-R2基因编码区和TRAIL-RI基因死亡区进行了突变检测。总体而言，发现8个肿瘤（6.8%）有2个TRAIL-RI基因突变或6个TRAIL-R2基因突变。有趣的是，在8个突变中，在死亡结构域中检测到6个错义突变（2个TRAIL-R1和4个TRAIL-R2），并且在死亡结构域之前检测到TRAIL-R2的1个无义突变。提示TRAIL-R1和TRAIL-R2基因的体细胞突变可能在某些NHL的发病机制中起一定作用，TRAIL-R2和TRAIL-R2基因可能是NHL中染色体8 p21 -22丢失的相关基因。
Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R1) and tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) are cell-surface receptors involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-RI and TRAIL-R2 genes have recently been mapped to chromosome 8p21-22, which is a frequent site of allelic deletions in many types of human tumors, including non-Hodgkin's lymphoma (NHL), Because TRAIL/TRAIL, receptor system plays an important role in lymphocyte homeostasis, we hypothesized that the mutations of TRAIL-RI and TRAIL-R2 may be involved in the development of NHL and that such mutations may be responsible for the allelic losses of 8p21-22 in NHL, In this study, we analysed the entire coding region of TRAIL-R2 gene and the death domain region of TRAIL-RI gene for the detection of the somatic mutations in a series of 117 human NHLs using polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-RI gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight mutations, six missense mutations (two TRAIL-RI and four TRAIL-R2) were detected in the death domains and one nonsense mutation of TRAIL-R2 was detected just before the death domain. Our data suggest that somatic mutations of TRAIL-RI and TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TRAIL-R2 and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome 8p21-22 in human NHL.