A novel fusion gene PLEKHA6-NTRK3 in langerhans cell histiocytosis

Int J Cancer. 2019 Jan 1;144(1):117-124. doi: 10.1002/ijc.31636. Epub 2018 Oct 26.


Langerhans cell histiocytosis (LCH) is the most common histiocytosis with constitutive activation of the RAS-RAF-MEK-ERK (MAPKinase) cell signaling pathway. We analyzed 89 cases of BRAF and MAP2K1 mutations by Sanger sequencing, of which 18 cases showed that these two gene mutations are negative. Whole genome sequencing of suitable specimens in these negative cases revealed a translocation from the 3 intron of PLEKHA6 to the 13 intron of NTRK3 in one case. We identified that this translocation could cause a novel fusion mutation, PLEKHA6-NTRK3. Overexpression of the PLEKHA6-NTRK3 mutant in NIH 3T3 cells enhanced MAPKinase pathway activation, promote cell growth. Our result suggested that a new mutation need be included in LCH molecular screening panel to better define its prevalence in LCH.

Keywords: Erk pathway; PLEKHA6-NTRK3; fusion mutation; langerhans cell histiocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Cell Proliferation / genetics
  • Child
  • Child, Preschool
  • Female
  • Histiocytosis, Langerhans-Cell / genetics*
  • Histiocytosis, Langerhans-Cell / pathology
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Mice
  • Mutation
  • NIH 3T3 Cells
  • Receptor, trkC / genetics*
  • Recombinant Fusion Proteins / genetics*


  • Intracellular Signaling Peptides and Proteins
  • PLEKHA6 protein, human
  • Recombinant Fusion Proteins
  • Receptor, trkC