Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis
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.
|Authors||Azorsa, DO, Lee, DW, Wai, DH, Bista, R, Patel, AR, Aleem, E, Henry, MM and Arceci, RJ|
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.
|Journal||Pediatric Blood and Cancer|
|Journal citation||65 (9), pp. e27237-e27237|
|Digital Object Identifier (DOI)||doi:10.1002/pbc.27237|
|16 May 2018|
|Publication process dates|
|Deposited||12 Dec 2018|
|Accepted||17 Apr 2018|
|Accepted author manuscript|
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