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.
Abstract
MAPK alterations are present in most lesions from adult pulmonary LCH patients. In patients with refractory progressive disease, the identification of these alterations, including BRAF deletions, is important to guide the choice of targeted treatment. http://bit.ly/2Qoknsn
Footnotes
This article has supplementary material available from erj.ersjournals.com
Support statement: This study was supported by a grant from the Legs Poix 2016 Chancellerie des Universités de Paris, France. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: F. Jouenne has nothing to disclose.
Conflict of interest: S. Chevret has nothing to disclose.
Conflict of interest: E. Bugnet has nothing to disclose.
Conflict of interest: E. Clappier has nothing to disclose.
Conflict of interest: G. Lorillon reports travel/accommodation from Vitalaire and Chiesi, outside the submitted work.
Conflict of interest: V. Meignin has nothing to disclose.
Conflict of interest: A. Sadoux has nothing to disclose.
Conflict of interest: S. Cohen has nothing to disclose.
Conflict of interest: A. Haziot has nothing to disclose.
Conflict of interest: A. How-Kit has nothing to disclose.
Conflict of interest: C. Kannengiesser has nothing to disclose.
Conflict of interest: C. Lebbé reports personal fees for consultancy, lectures and advisory board work from Amgen, grants and personal fees for consultancy, lectures, advisory board work and travel to meetings from BMS, grants and personal fees for consultancy, advisory board work and travel to meetings from MSD, grants and personal fees for consultancy, lectures and advisory board work from Roche and Novartis, personal fees for consultancy from Pierre Fabre, Sanofi and Merck Serono, and personal fees from Pfizer and Incyte, outside the submitted work.
Conflict of interest: D. Gossot reports personal fees from Delacroix-Chevalier (instrument manufacturer), outside the submitted work.
Conflict of interest: S. Mourah reports consultancy for Novartis and Roche, outside the submitted work.
Conflict of interest: A. Tazi reports personal fees for lectures from BMS and travel/accommodation fees from Boehringer Ingelheim, Teva, Vitalaire and AstraZeneca, outside the submitted work.
- Received June 17, 2019.
- Accepted November 13, 2019.
- Copyright ©ERS 2020
INDIVIDUALS
Log in using your username and password
LIBRARY USERS
Log in through your institution
Purchase access
CONTACT US
If you have any questions about the ERS publications website, please contact journals@ersnet.org