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BRAFV600E and MAP2K1 mutations in Langerhans cell histiocytosis occur predominantly in children.
Hematological Oncology 2017 December
Langerhans cell histiocytosis (LCH) is a proliferative disease of CD1a+ /CD207+ dendritic cells. Recurrent BRAFV600E and MAP2K1 mutations have been reported in LCH. To investigate the relationship among the mutation, clinical findings, and differentiation status of LCH, respectively, we studied 97 cases of LCH by using Sanger sequencing and immunohistochemistry. The mutually exclusive BRAFV600E and MAP2K1 mutation rates were 32% and 17.5%, respectively. All MAP2K1 mutations were missense mutations without any in-frame deletions; 2 new recurrent missense mutations (ie, p.E38K and p.P105S) were also found. More BRAFV600E and MAP2K1 mutations occurred in children compared with those in adult patients (P = .001), and BRAF mutation was correlated with relapse (P = .009). To the differentiation-related markers, the BRAF/MAP2K1-mut LCH expressed CD14 but rarely expressed CD83 or CD86 (P < .001). On the contrary, BRAF/MAP2K1-wt LCH cells rarely expressed CD14 but expressed CD86, and some also expressed CD83 (P < .001). This indicated that the BRAF/MAP2K1-mut LCH cells had a more immature state than BRAF/MAP2K1-wt LCH cells. Moreover, we also found the BRAFV600E and MAP2K1 mutations were significantly associated with pERK expression (P < .001). Therefore, the RAS/RAF/MEK/ERK pathway might play a more important role in children than in adult patients with LCH.
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