Selway Joanne Louise, Harikumar Parvathy Elacode, Chu Anthony, Langlands Kenneth
Medical School, University of Buckingham, Buckingham MK18 1EG, UK.
Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
Oncol Lett. 2017 Oct;14(4):4449-4454. doi: 10.3892/ol.2017.6774. Epub 2017 Aug 18.
Langerhans cell histiocytosis (LCH) is a heterologous disease with a recognized disparity in incidence, affected sites and prognosis between adults and children. The recent identification of BRAF mutations in LCH prompted the investigation of the frequency of these mutations in adult and childhood disease with the involvement of single or multiple sites in the present study. The study analysed the BRAF status in a cohort of adult LCH patients by DNA sequencing, and performed a broader meta-analysis of BRAF mutations in LCH in order to investigate any association with disease site and severity. A review of the literature revealed that ~47% of lesions from cases of adult disease (patient age, >18 years) were V600E-positive compared with 53% in those under 18 years. When single and multiple site disease was compared, there was a slight increase in the former (61 vs. 51%, respectively). A greater difference was observed when high- and low-risk organs were compared; for example, 75% of liver biopsies (a high-risk organ) were reported to bear the mutation compared with 47% of lung biopsies. In the adult LCH population, DNA sequencing identified mutations in 38% of 29 individuals, which is slightly lower than the figure identified from the meta-analysis (in which a total of 132 individuals were sampled), although we this value could not be broken down by clinical status. Thus, V600E status at presentation in itself is not predictive of tumour course, but a considerable proportion of LCH patients may respond to targeted V600E therapies.
朗格汉斯细胞组织细胞增多症（LCH）是一种异质性疾病，在成人和儿童之间，其发病率、受累部位及预后存在公认的差异。最近在LCH中发现的BRAF突变促使人们在本研究中调查这些突变在成人和儿童疾病中累及单个或多个部位时的发生频率。该研究通过DNA测序分析了一组成人LCH患者的BRAF状态，并对LCH中的BRAF突变进行了更广泛的荟萃分析，以研究其与疾病部位和严重程度的任何关联。文献综述显示，成人疾病（患者年龄>18岁）病例中约47%的病变为V600E阳性，而18岁以下患者中这一比例为53%。当比较单部位和多部位疾病时，前者略有增加（分别为61%和51%）。在比较高风险和低风险器官时观察到更大差异；例如，据报道75%的肝活检（高风险器官）存在该突变，而肺活检的这一比例为47%。在成人LCH人群中，DNA测序在29名个体中的38%发现了突变，这略低于荟萃分析确定的数字（共抽样132名个体），尽管我们无法按临床状态对该值进行细分。因此，初诊时的V600E状态本身并不能预测肿瘤病程，但相当一部分LCH患者可能对靶向V600E治疗有反应。
