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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jul 27, 2017
Source ID
10.1002/pbc.26699

Entities

People

  • Benjamin H. Durham
  • David C. Lyden
  • Ehud Lavi
  • Eli L Diamond
  • Ira J. Dunkel
  • Mario E. Lacouture
  • Neerav N Shukla
  • Omar Abdel‐wahab
  • Pallavi Khattar
  • Ryma Benayed
  • Sara Zarnegar

Organizations

  • American Society of Hematology
  • CURE Childhood Cancer
  • Damon Runyon Cancer Research Foundation
  • Edward P. Evans Foundation
  • Histiocytosis Association
  • Memorial Sloan Kettering Cancer Center
  • National Heart, Lung, and Blood Institute
  • National Institutes of Health
  • The Starr Foundation
  • United States Department of Defense
  • Weill Cornell Medicine

Tags

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Immunology
  • Molecular and Cellular Biology