Genomic Alterations in Langerhans Cell Histiocytosis

Barrett J Rollins

doi:10.1016/j.hoc.2015.06.004

Genomic Alterations in Langerhans Cell Histiocytosis

Hematol Oncol Clin North Am. 2015 Oct;29(5):839-51. doi: 10.1016/j.hoc.2015.06.004.

Author

Barrett J Rollins¹

Affiliation

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: barrett_rollins@dfci.harvard.edu.

PMID: 26461146
DOI: 10.1016/j.hoc.2015.06.004

Abstract

The discovery of recurrent somatic genomic alterations in Langerhans cell histiocytosis (LCH) has led to a new understanding of LCH as a clonal neoplastic disorder. Most of the abnormalities described to date affect the RAS/RAF/MEK/extracellular-signal-regulated kinase (ERK) pathway: more than 50% of LCH cases carry activating mutations in BRAF, whereas another 10% to 28% carry activating mutations of MAP2K1, which encodes MEK1. The pathogenetic importance of these mutations has been confirmed by reports of significant clinical responses to RAF inhibitors.

Keywords: BRAF; LCH; Langerhans cell histiocytosis; MAP2K1; MEK1.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Genetic Predisposition to Disease*
Genetic Variation*
Histiocytosis, Langerhans-Cell / diagnosis
Histiocytosis, Langerhans-Cell / drug therapy
Histiocytosis, Langerhans-Cell / genetics*
Histiocytosis, Langerhans-Cell / metabolism
Humans
MAP Kinase Signaling System
Molecular Targeted Therapy
Mutation