Genetic homogeneity of adult Langerhans cell histiocytosis lesions: Insights from BRAFV600E mutations in adult populations

Selway,Joanne  Louise; Harikumar,Parvathy  Elacode; Chu,Anthony; Langlands,Kenneth

doi:10.3892/ol.2017.6774

Genetic homogeneity of adult Langerhans cell histiocytosis lesions: Insights from BRAFV600E mutations in adult populations

Authors:
- Joanne Louise Selway
- Parvathy Elacode Harikumar
- Anthony Chu
- Kenneth Langlands
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Affiliations: Medical School, University of Buckingham, Buckingham MK18 1EG, UK, Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK
Published online on: August 18, 2017 https://doi.org/10.3892/ol.2017.6774
Pages: 4449-4454
Copyright: © Selway et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Langerhans cell histiocytosis (LCH) is a heterologous disease with a recognized disparity in incidence, affected sites and prognosis between adults and children. The recent identification of BRAFV600E mutations in LCH prompted the investigation of the frequency of these mutations in adult and childhood disease with the involvement of single or multiple sites in the present study. The study analysed the BRAFV600E status in a cohort of adult LCH patients by DNA sequencing, and performed a broader meta‑analysis of BRAFV600E mutations in LCH in order to investigate any association with disease site and severity. A review of the literature revealed that ~47% of lesions from cases of adult disease (patient age, >18 years) were V600E-positive compared with 53% in those under 18 years. When single and multiple site disease was compared, there was a slight increase in the former (61 vs. 51%, respectively). A greater difference was observed when high- and low-risk organs were compared; for example, 75% of liver biopsies (a high-risk organ) were reported to bear the mutation compared with 47% of lung biopsies. In the adult LCH population, DNA sequencing identified mutations in 38% of 29 individuals, which is slightly lower than the figure identified from the meta-analysis (in which a total of 132 individuals were sampled), although we this value could not be broken down by clinical status. Thus, V600E status at presentation in itself is not predictive of tumour course, but a considerable proportion of LCH patients may respond to targeted V600E therapies.

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