Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis

Patients with Langerhans cell histiocytosis (LCH) harbor BRAF V600E and activating mutations of MAP2K1/MEK1 in 50% and 25% of cases, respectively. We evaluated a patient with treatment‐refractory LCH for mutations in the RAS‐RAF‐MEK‐ERK pathway and identified a novel mutation in the MAP2K1 gene resulting in a p.L98_K104 > Q deletion and predicted to be auto‐activating. During treatment with the MEK inhibitor trametinib, the patient's disease showed significant progression. In vitro characterization of the MAP2K1 p.L98_K104 > Q deletion confirmed its effect on cellular activation of the ERK pathway and drug resistance.

This is the peer reviewed version of the following article: Azorsa, D.O., Lee, D.W., Wai, D.H., Bista, R., Patel, A.R., Aleem, E., Henry, M.M., and Arceci, R.J. (2018). Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis. Pediatric Blood & Cancer, 65(9), e27237-e27237. doi: https://www.doi.org/10.1002/pbc.27237, which has been published in final form at https://www.doi.org/10.1002/pbc.27237. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.