Gale and Ira Drukier Institute for Children's Health

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Novel activating BRAF fusion identifies a recurrent alternative mechanism for ERK activation in pediatric Langerhans cell histiocytosis.

TitleNovel activating BRAF fusion identifies a recurrent alternative mechanism for ERK activation in pediatric Langerhans cell histiocytosis.
Publication TypeJournal Article
Year of Publication2018
AuthorsZarnegar S, Durham BH, Khattar P, Shukla NN, Benayed R, Lacouture ME, Lavi E, Lyden DC, Diamond EL, Dunkel IJ, Abdel-Wahab O
JournalPediatr Blood Cancer
Volume65
Issue1
Date Published2018 Jan
ISSN1545-5017
KeywordsAdaptor Proteins, Signal Transducing, Child, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Histiocytosis, Langerhans-Cell, Humans, Male, Oncogene Proteins, Fusion, Proto-Oncogene Proteins B-raf
Abstract

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by constitutive activation of extracellular signal-regulated kinase (ERK). Genomic characterization has identified activating point mutations including mutually exclusive BRAFV600E and activating MAP2K1 mutations to be responsible for ERK activation in a majority of pediatric LCH patients. Here, we report the discovery of a novel BRAF kinase fusion, PACSIN2-BRAF, in a child with multisystem LCH. This is the second reported case of an activating BRAF kinase fusion and indicates a recurrent pathologic mechanism. Genomic evaluation for activating kinase fusions should be strongly considered in pediatric LCH patients lacking more common mutations.

DOI10.1002/pbc.26699
Alternate JournalPediatr Blood Cancer
PubMed ID28748614