Clinicogenomic associations in patients with Langerhans cell histiocytosis: a cohort study

Abstract

This article presents an analysis of genotype and phenotype correlations in a pediatric cohort with Langerhans cell histiocytosis (LCH). Approximately 60% of LCH patients carry BRAF V600E somatic point mutation. Numerous studies have demonstrated that the presence of this mutation is associated with a more severe course of the disease and a higher risk of relapse. Apart from BRAF V600E mutation, other mutations in genes involved in the RAS/RAF/MEK/ERK signaling pathway have been identified in LCH. Next generation sequencing of DNA with high coverage of target regions is considered an optimal approach to detect somatic mutations other than BRAF V600E. The identification of somatic driver mutations holds great potential for enhancing our understanding of the phenotypic heterogeneity of LCH and developing targeted therapeutic strategies. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.