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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(P>0.05)。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 G>A 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。
Objective: To investigate the occurrence and clinical significance of BRAF V600E and MAP2K1 gene mutations in Langerhans cell histiocytosis (LCH) in China. Methods: 35 cases of LCH tissue samples were randomly selected. The mutation of BRAF V600E and MAP2K1 gene was detected by Sanger sequencing. The expression of BRAF V600E protein was detected by immunohistochemistry. To analyze the relationship between BRAF V600E, MAP2K1 gene mutations and basic clinical data of LCH (age, sex, single / multiple system). Results: In 35 patients with LCH, the male-to-female ratio was 1.7: 1 and 82.9% invaded bone tissue. 97.1% were single system LCH (SS-LCH) and 2.9% were multi-system LCH , MS-LCH). The mutation rate of BRAF V600E gene was 17.1%, the mutation rate of MAP2K1 gene was 14.3% and the mutation of MAP2K1 and BRAF V600E gene were mutually different. The positive rate of BRAF V600E by immunohistochemistry was 28.6% Mutation cases measured by sequencing. The BRAF V600E and MAP2 K1 gene mutations were more frequently seen in the juvenile group (35.7% and 28.6%). The BRAF V600E mutation was significantly different between the minor group and the adult group (P = 0.028). The BRAF V600E and MAP2K1 genes The effect of mutation on survival was not statistically different (P> 0.05). Conclusion: Most of LCH patients in our country 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 rates of mutation of BRAF V600E and MAP2K1 detected by Sanger method were lower than those reported in the West, with the two being different, accounting for 17.1% and 14.3% respectively. All MAP2K1 gene mutations are point mutations, there is no in-frame deletion mutation and found a new mutation site: c.112 G> A p.E38K; BRAF V600E and MAP2K1 gene mutations occur mainly in the minor group, suggesting that all ages The pathogenesis of LCH in the layer may be different, and it is likely that the RAS / RAF / MEK / ERK pathway plays a more important role in the LCH of minors; in addition, these two mutations have no effect on the survival of LCH.