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(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 study BRAF V600E and MAP2K1 gene mutations in Langerhans cell histiocytosis and analyze the relationship between the two mutations and clinical findings. Methods：Sanger sequencing was used to detect gcne mutations. Immunohistochemistry was used to detect BRAF V6OOE protein expression. X2 test was used to analyze the relation between mutations and clinical items （age, gender, single/multi -system disease, etc）. Results： Among 35 cases of Langerhans cell histiocytosis （LCH） the ratio between male and female was 1.7： 1. The primary site of bone were found in 82.9% of the cases. 97.1% of the cases belonged to single system disease and only 2.9% belonged to multiple system disease. The incidence rate of BARF V600E mutation was 17.1% ,while that of MAP2K1 mutation was 14.3%. The two mutations were mutually exclusive. The mutation of BRAF V6OOE detected by immunostaining was 28.6% which covered all mutated cases detected by Sanger sequencing. The incidence rate of BRAF V600E and MAP2K1 gene mutations was 35.7% and 28.6% respectively in under - age patients. The incidence rate of the two gene mutations （4.8%） was same in adult patients. Conclusion： LCH patients in our study mostly belonged to single system disease. The bone was mostly involved. The prognosis was good with 5 years survival of 97.1%. The incidence rate of BRAF V600E and MAP2K1 mutation was lower than that of western countries. The BRAF V600E mutation significantly occurred more in under - age patients than adult patients. All of the mutated MAP2K1 was point mutation without any in - framed deletion as reported by foreign country. The new point mutation was also found：c. 112 G 〉 A p. E38K. It may indicate that the pathogenetic mechanism maybe different in different age groups of LCH patients. The two mutations had no effect on survival.
出处
《现代肿瘤医学》
CAS
2016年第1期1-6,共6页
Journal of Modern Oncology
基金
国家自然科学基金资助项目(编号:81071951)
