Abstract
Langerhans cell histiocytosis (LCH) is characterized by mutations of the RAS-RAF-MAPK signaling pathway. We analyzed MAP2K1, NRAS and KIT mutation incidence in skin lesions of BRAF wild-type (wt) LCH patients. We evaluated the occurrence of MAP2K1, NRAS and KIT mutations in seven LCH and one indeterminate cell histiocytosis (ICH) patients. MAP2K1 mutation frequency was found to be 3/7 (42.9%) in LCH and also found in ICH. Similarly, the KIT mutation frequency was found to be equally prevalent (4/7, 57.1%) in LCH and also occurred in ICH. Involvement of KIT exons in LCH-ICH indicated that exon 9/11/18 were equally prevalent followed by exon 13. This exploratory analysis on BRAF-wt LCH revealed a KIT mutation rate comparable to MAP2K1. Although the detected KIT mutations are different from activating mutations found in other KIT-dependent neoplasms, our data suggest that KIT-inhibitors might have a role in treating BRAF-wt LCH patients.
Highlights
The revised classification scheme of the Histiocyte Society classified histiocytic disorders into five groups
It is of note that the indeterminate cell histiocytosis (ICH) tumor carried a mutant MAP2K1
KIT mutations were detected in four BRAF-wt Langerhans cell histiocytosis (LCH) samples out of seven (57.1%) and the ICH sample was positive for KIT mutation
Summary
The revised classification scheme of the Histiocyte Society classified histiocytic disorders into five groups. Group L (Langerhans) includes Langerhans cell histiocytosis (LCH), indeterminate cell histiocytosis (ICH), Erdheim-Chester disease (ECD) and mixed LCH/ECD [1]. The incidence of LCH, which is the most common histiocytic disease, is estimated to be between 4.6 and 9 cases per million children, while it is 1–2 cases per million adults [2]. The most frequent mutational driver in L type histocytoses is BRAF, which rarely affects ARAF. This is followed by frequent mutations of MAP2K1. Mutations rarely affect RAS itself (N- or H-) or the AKT-mTOR signaling pathway [1, 2]
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