霍奇金淋巴瘤中ΙκΒα基因突变的研究  

Mutation of IκBα gene in Hodgkins lymphoma:a prelimimary analysis

作　　者：刘晓健[1,2] 杨文涛[3,2] 周晓燕[3,2] 陆洪芬[3,2] 施达仁[3,2] 

机构地区：[1]复旦大学肿瘤医院化疗科 [2]复旦大学上海医学院肿瘤学系,上海200032 [3]复旦大学肿瘤医院病理科

出　　处：《临床与实验病理学杂志》2010年第2期168-172,共5页Chinese Journal of Clinical and Experimental Pathology

摘　　要：目的分析霍奇金淋巴瘤细胞中IκBα基因突变的特点、可能造成的蛋白结构异常,并探讨其分子病理学意义。方法应用激光显微切割技术分离16例霍奇金淋巴瘤切片中的HRS细胞,并对IκBα基因进行半巢式PCR扩增及DNA直接测序,检测HRS细胞IκBα基因6个外显子突变。结果16例标本中6例发现IκBα基因突变,突变率为37.5%,突变分别位于1、4、5和6外显子上。其中2例第五外显子出现点突变,形成TGA终止密码子;1例出现第四外显子单碱基缺失突变,形成框移,可造成IκBα蛋白羧基端缺失。霍奇金淋巴瘤背景中反应性淋巴细胞没有发现IκBα突变。结论霍奇金淋巴瘤IκBα基因突变率为37.5%,高于文献报道(10%～25%)。突变可能造成IκBα蛋白的结构异常,通常造成羧基端截短改变。背景中反应性增生的淋巴细胞未发现IκBα基因突变,表明IκBα的基因突变是HRS细胞的特征,并可能在霍奇金淋巴瘤发病机制中起重要作用。Purpose To examine the features of IκBα gene mutation possiblely led to the structural alterations in protein level and to explore its molecular pathological significance in Hodgkins lymphoma.Methods Individual HRS cells from lymph node biopsy samples from 16 CD30 positive patients with primary Hodgkins lymphoma were isolated from immunostained tissue sections by laser microdissection（LMD） and then used for semi-nested PCR amplification to obtain the exons Ⅰ～Ⅳ of IκBα gene.The resulted PCR products were gel-purified and sequenced.Results The mutations were all unique nucleotide exchanges or deletions.The rate of mutation of IκBα gene was 37.5%,located in the exons 1,4,5,and 6.Two of them having a point mutation in exon 5 generated a preterminal stop codon.One of them having deletion of one nucleotide led to frameshift.These three mutations all presumedly resulted in a C-terminally truncated form of the IκBα protein.No mutations were found in surround reactive cells.Conclusions 37.5% of the H/RS cells in the cases of Hodgkins lymphoma have mutations in the IκBα gene and possibly result in C-terminally truncated form of the IκBα protein,and the functional damage of the protein,suggesting that loss or severe impairment of the IκBα functions is produced during the pathogenesis of the tumor cell clone,obviously leading to constitutive nuclear activity of NF-κB.

关 键 词：霍奇金淋巴瘤 IΚBΑ 突变 激光显微切割技术 

分 类 号：R733.4[医药卫生—肿瘤] R730.21[医药卫生—临床医学]