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- Title
Circulating cell-free BRAF<sup>V600E</sup> as a biomarker in children with Langerhans cell histiocytosis.
- Authors
Héritier, Sébastien; Hélias ‐ Rodzewicz, Zofia; Lapillonne, Hélène; Terrones, Nathalie; Garrigou, Sonia; Normand, Corinne; Barkaoui, Mohamed ‐ Aziz; Miron, Jean; Plat, Geneviève; Aladjidi, Nathalie; Pagnier, Anne; Deville, Anne; Gillibert ‐ Yvert, Marion; Moshous, Despina; Lefèvre ‐ Utile, Alain; Lutun, Anne; Paillard, Catherine; Thomas, Caroline; Jeziorski, Eric; Nizard, Philippe
- Abstract
The BRAF V600E mutation is reported in half of patients with Langerhans cell histiocytosis ( LCH). This study investigated the detection of the BRAF V600E allele in circulating cell-free (ccf) DNA in a paediatric LCH cohort. Children with BRAFV600E-mutated LCH were investigated to detect ccf BRAF V600E at diagnosis ( n = 48) and during follow-up ( n = 17) using a picolitre-droplet digital PCR assay. At diagnosis, ccf BRAFV600E was positive in 15/15 (100%) patients with risk-organ positive multisystem ( RO+ MS) LCH, 5/12 (42%) of patients with RO− MS LCH and 3/21 (14%) patients with single-system ( SS) LCH ( P < 0·001, Fisher's exact test). The positive BRAFV600E load was higher for RO+ patients (mean, 2·90%; range, 0·04-11·4%) than for RO− patients (mean, 0·16%; range, 0·01-0·39) ( P = 0·003, Mann-Whitney U test). After first-line vinblastine-steroid induction therapy, 7/7 (100%) of the non-responders remained positive for ccf BRAFV600E compared to 2/4 (50%) of the partial-responders and 0/4 of the complete responders ( P = 0·002, Fisher's exact test). Six children treated with vemurafenib showed a clinical response that was associated with a decrease in the ccf BRAFV600E load at day 15. Thus, ccf BRAFV600E is a promising biomarker for monitoring the response to therapy for children with RO+ MS LCH or RO− LCH resistant to first-line chemotherapy.
- Subjects
LANGERHANS-cell histiocytosis; BIOMARKERS; ALLELES; GENETIC mutation; INTERSTITIAL lung diseases in children; GENETICS
- Publication
British Journal of Haematology, 2017, Vol 178, Issue 3, p457
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.14695