Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease Academic Article uri icon


MeSH Major

  • Erdheim-Chester Disease
  • GTP Phosphohydrolases
  • Membrane Proteins
  • Phosphatidylinositol 3-Kinases


  • Erdheim-Chester disease (ECD) is a rare histiocytic disorder that is challenging to diagnose and treat. We performed molecular analysis of BRAF in the largest cohort of ECD patients studied to date followed by N/KRAS, PIK3CA, and AKT1 mutational analysis in BRAF wild-type patients. Forty-six of 80 (57.5%) of patients were BRAFV600E-mutant. NRAS mutations were detected in 3 of 17 ECD BRAFV600E wild-type patients. PIK3CA mutations (p.E542K, p.E545K, p.A1046T, and p.H1047R) were detected in 7 of 55 patients, 4 of whom also had BRAF mutations. Mutant NRAS was present in peripheral blood CD14(+) cells, but not lymphoid cells, from an NRASQ61R mutant patient. Our results underscore the central role of RAS-RAF-MEK-ERK activation in ECD and identify an important role of activation of RAS-PI3K-AKT signaling in ECD. These results provide a rationale for targeting mutant RAS or PI3K/AKT/mTOR signaling in the subset of ECD patients with NRAS or PIK3CA mutations.

publication date

  • November 6, 2014



  • Academic Article



  • eng

PubMed Central ID

  • PMC4224196

Digital Object Identifier (DOI)

  • 10.1182/blood-2014-04-570937

PubMed ID

  • 25150293

Additional Document Info

start page

  • 3016

end page

  • 9


  • 124


  • 19