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Genetic landscape of adult Langerhans cell histiocytosis with lung involvement
- Source :
- European Respiratory Journal. 55:1901190
- Publication Year :
- 2019
- Publisher :
- European Respiratory Society (ERS), 2019.
-
Abstract
- The clinical significance of the BRAFV600E mutation in adult Langerhans cell histiocytosis (LCH), including pulmonary Langerhans cell histiocytosis (PLCH), is not well understood. Similarly, the spectrum of molecular alterations involved in adult LCH has not been fully delineated. To address these issues, we genotyped a large number of adult LCH biopsies and searched for an association of identified molecular alterations with clinical presentation and disease outcome.Biopsies from 117 adult LCH patients, 83 with PLCH (median age 36.4 years, 56 females, 38 multisystem disease, 79 single system disease, 65 current smokers) were genotyped for the BRAFV600E mutation. In 69 cases, LCH lesions were also genotyped by whole-exome sequencing (WES) or targeted gene panel next-generation sequencing (NGS). Cox models were used to estimate the association of baseline characteristics with the hazard of LCH progression.MAPK pathway alterations were detected in 59 out of 69 cases (86%) (BRAFV600E mutation: 36%, BRAFN486_P490 deletion: 28%, MAP2K1 mutations: 15%, isolated NRASQ61 mutations: 4%), while KRAS mutations were virtually absent in PLCH lesions. The BRAFV600E mutation was not associated with LCH presentation at diagnosis, including smoking status and lung function, in PLCH patients. BRAFV600E status did not influence the risk of LCH progression over time.Thus, MAPK alterations are present in most lesions from adult LCH patients, particularly in PLCH. Unlike reports in paediatric LCH, BRAFV600E genotyping did not provide additional information on disease outcome. The search for alterations involved in the MAPK pathway, including BRAF deletions, is useful for guiding targeted treatment in selected patients with refractory progressive LCH.
- Subjects :
- Adult
Proto-Oncogene Proteins B-raf
0301 basic medicine
Pulmonary and Respiratory Medicine
Pathology
medicine.medical_specialty
Disease
Adult Langerhans Cell Histiocytosis
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
MAP2K1
medicine
Humans
Clinical significance
Child
Lung
Genotyping
Mutation
business.industry
Proportional hazards model
High-Throughput Nucleotide Sequencing
Histiocytosis, Langerhans-Cell
030104 developmental biology
030220 oncology & carcinogenesis
Female
KRAS
business
Subjects
Details
- ISSN :
- 13993003 and 09031936
- Volume :
- 55
- Database :
- OpenAIRE
- Journal :
- European Respiratory Journal
- Accession number :
- edsair.doi.dedup.....bd8d71fca3732aba188217ba53780cb7
- Full Text :
- https://doi.org/10.1183/13993003.01190-2019