朗格汉斯细胞组织细胞增生症中BRAF V600E和MAP2K1基因突变的分析及其临床意义

发布时间：2018-05-29 05:14

本文选题：BRAF + VE　；参考：《现代肿瘤医学》2016年01期

【摘要】：目的:探讨我国朗格汉斯细胞组织细胞增生症(Langerhans cell histiocytosis,LCH)中BRAF V600E和MAP2K1基因突变发生状况及其临床意义。方法:随机选取35例LCH组织标本,采用桑格测序法检测其中BRAF V600E和MAP2K1基因突变状况,免疫组化法检测BRAF V600E蛋白的表达。分析BRAF V600E、MAP2K1基因突变与LCH临床基本资料(年龄、性别、单/多系统)的关系。结果:在35例LCH患者中,男女比例为1.7∶1,82.9%侵及骨组织,97.1%是单系统LCH(single system LCH,SS-LCH),2.9%是多系统LCH(multi-system LCH,MS-LCH)。桑格测序法检测BRAF V600E基因突变率为17.1%,MAP2K1基因突变率为14.3%,MAP2K1与BRAF V600E基因突变有互异性;免疫组化法检测BRAF V600E阳性表达率为28.6%,涵盖了桑格测序法测得的突变病例。BRAF V600E和MAP2 K1基因突变更多出现在未成年组(35.7%和28.6%),其中BRAF V600E突变在未成年人组与成人组间有显著性差异(P=0.028);BRAF V600E和MAP2K1基因突变对生存的影响无统计学差异(P0.05)。结论:我国LCH患者大部分都是SS-LCH,主要侵及的部位是骨组织,且预后良好,5年生存率为97.1%。桑格法所测的BRAF V600E和MAP2K1基因突变率均低于西方报道,两者存在互异性,分别为17.1%和14.3%。所有MAP2K1基因突变都是点突变,没有框内缺失突变,发现一个新的突变位点:c.112 GA p.E38K;BRAF V600E和MAP2K1基因突变主要发生于未成年组中,提示各年龄层中LCH的发病机理可能不同,可能RAS/RAF/MEK/ERK通路在未成年人LCH中发挥更重要的作用;另外这两种突变对LCH的生存无影响。
[Abstract]:Objective: to investigate the mutation status of BRAF V600E and MAP2K1 gene in Langerhans cell histiocytosis LCHs in China and its clinical significance. Methods: 35 LCH tissue samples were randomly selected and the mutation status of BRAF V600E and MAP2K1 gene were detected by Sanger sequencing method. The expression of BRAF V600E protein was detected by immunohistochemistry. To analyze the relationship between BRAF V600Emap2K1 gene mutation and basic clinical data (age, sex, single / multi-system) of LCH. Results: in 35 patients with LCH, the ratio of male and female was 1.7: 1%, 82.9% was involved in bone tissue, 97.1% was single system LCH(single system LCHSS-LCHS, 2.9% was multisystem LCH(multi-system LCHS-LCHS. The mutation rate of BRAF V600E gene was 17.1and the mutation rate of MAP2K1 gene was 14.3MAP2K1 with BRAF V600E gene mutation. The positive expression rate of BRAF V600E detected by immunohistochemical method was 28.60.It covers the mutation cases of BRAF V600E and MAP2 K1 detected by Sanger sequencing. The mutation of BRAF V600E and MAP2 K1 is more common in the minor group (35.7%) and in the minor group (28.662%), among which the BRAF V600E mutation is found between the minor group and the adult group. There was no significant difference in the effect of BRAF V600E and MAP2K1 gene mutation on survival. Conclusion: the majority of LCH patients in China are SS-LCH.The main site of invasion is bone tissue, and the prognosis is good. The 5-year survival rate is 97.1%. The mutation rates of BRAF V600E and MAP2K1 genes measured by Sanger method were lower than those reported in the west, and there was mutual heterogeneity between them (17.1% and 14.3%, respectively). All the mutations of MAP2K1 gene were point mutations, and there was no deletion mutation in the box. A new mutation locus: c.112GA p.E38KnBRAF V600E and MAP2K1 gene mutations were found mainly in minor groups, suggesting that the pathogenesis of LCH may be different in different age groups. It is possible that the RAS/RAF/MEK/ERK pathway plays a more important role in the LCH of minors, and the other two mutations have no effect on the survival of LCH.
【作者单位】：第四军医大学病理学教研室;第四军医大学西京医院病理科;
【基金】：国家自然科学基金资助项目(编号:81071951)
【分类号】：R597

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