Osborne Julie, Lake Annette, Alexander Freda E, Taylor G Malcolm, Jarrett Ruth F
LRF Virus Centre, Institute of Comparative Medicine, University of Glasgow, Glasgow, United Kingdom.
Int J Cancer. 2005 Sep 10;116(4):646-51. doi: 10.1002/ijc.21036.
Somatic inactivation of NFKBIA, the gene encoding IkappaBalpha, is a frequent occurrence in the malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL). Impairment of IkappaBalpha function results in deregulated NF-kappaB activity, a characteristic of HRS cells. The molecular basis for familial HL, which accounts for approximately 4% of all HL cases, is unclear. To date, familial HL cases have not been evaluated for germline NFKBIA mutations. We screened the entire NFKBIA gene in 8 individuals with familial HL but found no mutations in the coding region or promoter sequences. We identified the first germline NFKBIA missense mutation in a patient with presumed sporadic HL. The frequency of 4 polymorphisms within the NFKBIA gene and promoter region was investigated in a series of HL and control samples; no significant differences emerged but a novel polymorphism was identified in the promoter region. Overall, our results suggest that germline mutations of NFKBIA are not a significant cause of familial aggregation of HL but may contribute to inherited susceptibility to HL.
NFKBIA（编码IkappaBalpha的基因）的体细胞失活在霍奇金淋巴瘤（HL）的恶性霍奇金和里德-斯特恩伯格（HRS）细胞中经常发生。IkappaBalpha功能受损导致NF-κB活性失调，这是HRS细胞的一个特征。占所有HL病例约4%的家族性HL的分子基础尚不清楚。迄今为止，尚未对家族性HL病例进行种系NFKBIA突变评估。我们对8例家族性HL患者的整个NFKBIA基因进行了筛查，但在编码区或启动子序列中未发现突变。我们在一名疑似散发型HL患者中鉴定出首个种系NFKBIA错义突变。在一系列HL和对照样本中研究了NFKBIA基因和启动子区域内4种多态性的频率；未发现显著差异，但在启动子区域鉴定出一种新的多态性。总体而言，我们的结果表明，NFKBIA的种系突变不是HL家族聚集的重要原因，但可能导致对HL的遗传易感性。
