RT期刊文章SR电子T1经常性Nras肺Langerhans细胞组织细胞增多的突变JF欧洲呼吸杂志JO EUR RESSIR J FD欧洲呼不188bet官网地址A1 Lorillon, Gwenaël A1 Bugnet, Emmanuelle A1 Mauger, Florence A1 Lebbe, Celeste A1 Chevret, Sylvie A1 Tost, Jörg A1 Tazi, Abdellatif YR 2016 UL //www.qdcxjkg.com/content/47/6/1785.abstractAB在Langerhans细胞组织细胞增多症（LCH）中不断激活有丝分裂原激活的蛋白激酶（MAPK）途径。下游激酶BRAF和MAP2K1的突变介导了LCH病变子集中的这种激活。在这项研究中，我们试图鉴定其他突变，这些突变可能解释了未突破的BRAF和MAP2K1 LCH病变中的MAPK激活。我们分析了26个肺和37个非肺LCH病变，用于BRAF，MAP2K1，NRAS，NRAS和KRAS突变。来自10名吸烟者患者的严重正常肺组织被用作对照。同时评估了患者的自发性结果。分别观察到BRAFV600E突变分别在50％和38％的肺和非肺LCH病变中观察到。40％的肺LCH病变具有NRASQ61K/R突变，而在非肺LCH活检或肺组织对照中未发现NRAS突变。在11个NRASQ61K/R-突变的肺LCH病变中的7个中，也存在BRAFV600E突变。分别从相同的肺LCH病变中分别基因分型，表明这些并发的BRAF和NRAS突变是由不同的细胞克隆携带的。 NRASQ61K/R mutations activated both the MAPK and AKT (protein kinase B) pathways. In the univariate analysis, the presence of concurrent BRAFV600E and NRASQ61K/R mutations was significantly associated with patient outcome.These findings highlight the importance of NRAS genotyping of pulmonary LCH lesions because the use of BRAF inhibitors in this context may lead to paradoxical disease progression. These patients might benefit from MAPK kinase inhibitor-based treatments.Pulmonary Langerhans cell histiocytosis genetic landscape includes recurrent activating NRAS Q61 mutations http://ow.ly/YgsSm