Ty-Jour T1 - 逆转 NRAS 肺朗格汉斯细胞组织菌均突变JF - 欧洲呼吸杂志Jo - Eur Respir J SP - 1785 LP - 1796 Do - 10.1183 / 13993003.01677-2015 VL - 47是 - 6 Au- Mourah，Samia Au - alexandre au - Meignin，Véroniqueau - Gossot，Dominique Au - Lorillon，GwenaëlAu - Bugnet，Emmanuelle Au - Mauger，Florence Au - Lebbe，Celeste Au - Chevret，Sylvie Au - Tost，JörgAu - 塔齐，阿卜杜勒省Y1 - 2016/06/01 UR - //www.qdcxjkg.com/content/47/6/1785.abstract n2 - 丝裂剂活化的蛋白激酶（mapk）途径不断被激活Langerhans细胞组织菌症（LCH）。下游激酶BRAF和MAP2K1的突变在LCH病变的子集中介导该活化。在本研究中，我们试图识别其他突变，该突变可以解释非融合BRAF和MAP2K1 LCH病变中的MAPK激活。我们分析了26例肺和37个非玻璃LCH病变，用于BRAF，MAP2K1，NRA和KRAS突变。来自10名吸烟者患者的严重正常肺组织用作对照。患者同时评估自发性结果。分别以50％和38％的肺和非玻利菌落病变观察到Brafv600e突变。40％的肺部LCH病变患有NRASQ61K / R突变，而在非胆碱LCH活检或肺组织对照中不鉴定NRAS突变。在11个NRASQ61K / R型突变的肺LCH病变中，还存在BRAFV600E突变。 Separately genotyping each CD1a-positive area from the same pulmonary LCH lesion demonstrated that these concurrent BRAF and NRAS mutations were carried by different cell clones. 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 ER -