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

Journal article


Azorsa, DO, Lee, DW, Wai, DH, Bista, R, Patel, AR, Aleem, E, Henry, MM and Arceci, RJ (2018). Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis. Pediatric Blood and Cancer. 65 (9), pp. e27237-e27237. https://doi.org/10.1002/pbc.27237
AuthorsAzorsa, DO, Lee, DW, Wai, DH, Bista, R, Patel, AR, Aleem, E, Henry, MM and Arceci, RJ
Abstract

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.

Year2018
JournalPediatric Blood and Cancer
Journal citation65 (9), pp. e27237-e27237
PublisherWiley
ISSN1545-5009
Digital Object Identifier (DOI)https://doi.org/10.1002/pbc.27237
Publication dates
Print16 May 2018
Publication process dates
Deposited12 Dec 2018
Accepted17 Apr 2018
Accepted author manuscript
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File Access Level
Open
Additional information

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.

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