Promiscuous mutations activate the noncanonical NF-κB pathway in multiple myeloma
Promiscuous mutations activate the noncanonical NF-κB pathway in multiple myeloma
复制标题
DOI：
10.1016/j.ccr.2007.07.003
复制
发表时间：
2007-08-01
期刊：
影响因子：
50.3
通讯作者：
Bergsagel, P. Leif
中科院分区：
文献类型：
--
作者：
Keats, Jonathan J.;Fonseca, Rafael;Bergsagel, P. Leif
nf - κ B的活化已在许多肿瘤类型中被注意到，但很少与潜在的基因突变有关。对155个多发性骨髓瘤样本的高密度寡核苷酸阵列CGH和基因表达谱数据的综合分析发现，在大约20%的患者中，混杂的异常阵列导致nf - κ B失调。我们报道了10个基因的突变，导致TRAF2、TRAF3、CYLD、cIAP1/cIAP2失活，NFKB1、NFKB2、CD40、LTBR、TACI和NIK的激活，主要导致非规范NF-kappa B通路的组成性激活，其中最常见的异常是TRAF3失活。这些结果强调了nf - κ B通路在多发性骨髓瘤发病机制中的关键重要性。
Activation of NF-kappa B has been noted in many tumor types, however only rarely has this been linked to an underlying genetic mutation. An integrated analysis of high-density oligonucleotide array CGH and gene expression profiling data from 155 multiple myeloma samples identified a promiscuous array of abnormalities contributing to the dysregulation of NF-kappa B in approximately 20% of patients. We report mutations in ten genes causing the inactivation of TRAF2, TRAF3, CYLD, cIAP1/cIAP2 and activation of NFKB1, NFKB2, CD40, LTBR, TACI, and NIK that result primarily in constitutive activation of the noncanonical NF-kappa B pathway, with the single most common abnormality being inactivation of TRAF3. These results highlight the critical importance of the NF-kappa B pathway in the pathogenesis of multiple myeloma.