Analysis of the BRAF and MAP2K1 mutations in patients with Langerhans cell histiocytosis in Japan

In Langerhans cell histiocytosis (LCH), somatic gene mutations in the mitogen-activated protein kinase pathway have been identified in more than 80% of cases in Western countries, in which mutually exclusiveBRAFandMAP2K1mutations are involved. Among them,BRAFV600E mutation is the major contributor (50-60%). In 59 patients (50 children and nine adults) with LCH (not including pulmonary LCH) in Japan, we first screened forBRAFV600E in all patients followed by target sequencing for other gene mutations in 17 ofBRAFV600E-negative patients. As a result,BRAFV600E mutation was detected in 27/59 (46%) patients. We also identifiedBRAFmutations other than V600E in five andMAP2K1mutations in nine patients. Thus, gene mutations inBRAForMAP2K1were identified in 41/44 (93%) of the fully tested patients. Regarding the correlation of clinical features and genotype in pediatric patients, we found thatBRAFV600E mutation status was not correlated with sex, age at diagnosis, disease extent, response to first-line therapy, relapse, or CNS-related sequelae. Interestingly,MAP2K1exon 2 in-frame deletion was related to the risk organ involvement; however, further studies are required to clarify the impact of these gene mutations on the clinical features of patients with LCH.