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


Authors: Zarnegar, S.; Durham, B. H.; Khattar, P.; Shukla, N. N.; Benayed, R.; Lacouture, M. E.; Lavi, E.; Lyden, D. C.; Diamond, E. L.; Dunkel, I. J.; Abdel-Wahab, O.
Article Title: Novel activating BRAF fusion identifies a recurrent alternative mechanism for ERK activation in pediatric Langerhans cell histiocytosis
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. © 2017 Wiley Periodicals, Inc.
Keywords: immunohistochemistry; mitogen activated protein kinase; child; clinical article; controlled study; human tissue; preschool child; unclassified drug; oncoprotein; gene mutation; human cell; promoter region; genetics; prednisone; clinical trial; case report; pathophysiology; genetic analysis; mitogen activated protein kinase kinase 1; skin defect; protein; enzyme activation; in vitro study; mutational analysis; vinblastine; bone lesion; oncogene proteins, fusion; mitogen activated protein kinase 1; adaptor proteins, signal transducing; extracellular signal-regulated map kinases; point mutation; epidermal growth factor receptor 3; signal transducing adaptor protein; b raf kinase; braf; genomic dna; proto-oncogene proteins b-raf; braf protein, human; langerhans cell histiocytosis; myeloid neoplasia; vemurafenib; histiocytosis, langerhans-cell; dabrafenib; trametinib; t6 antigen; humans; human; male; priority journal; article; kinase fusion; cobimetinib; lch; pacsin2; pacsin2 protein; pacsin2 protein, human
Journal Title: Pediatric Blood and Cancer
Volume: 65
Issue: 1
ISSN: 1545-5009
Publisher: Wiley Periodicals, Inc  
Date Published: 2018-01-01
Start Page: e26699
Language: English
DOI: 10.1002/pbc.26699
PUBMED: 28748614
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
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MSK Authors
  1. Mario E Lacouture
    261 Lacouture
  2. Ira J Dunkel
    251 Dunkel
  3. David C Lyden
    83 Lyden
  4. Neerav Shukla
    69 Shukla
  5. Eli Louis Diamond
    83 Diamond
  6. Rym Benayed
    68 Benayed
  7. Benjamin Heath Durham
    60 Durham