Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis
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Final Accepted Manuscript
Affiliation
University of Arizona College of Medicine - PhoenixIssue Date
2018-09-01Metadata
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Wiley PeriodicalsCitation
Azorsa, D. O., Lee, D. W., Wai, D. H., Bista, R., Patel, A. R., Aleem, E., ... & 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.Journal
Pediatric Blood & CancerRights
© 2018 Wiley Periodicals, Inc.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.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.Note
12 month embargo; first published: 16 May 2018ISSN
1545-5017PubMed ID
29768711Version
Final accepted manuscriptSponsors
Sharon D. Lund Foundation; University of Arizona COM-P Department of Child Health Mission Support; Phoenix Children's Hospital FoundationAdditional Links
https://onlinelibrary.wiley.com/doi/full/10.1002/pbc.27237https://www.ncbi.nlm.nih.gov/pubmed/29768711