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Circulating cell‐free BRAF V600E as a biomarker in children with Langerhans cell histiocytosis
Author(s) -
Héritier Sébastien,
HéliasRodzewicz Zofia,
Lapillonne Hélène,
Terrones Nathalie,
Garrigou Sonia,
Normand Corinne,
Barkaoui MohamedAziz,
Miron Jean,
Plat Geneviève,
Aladjidi Nathalie,
Pagnier Anne,
Deville Anne,
GillibertYvert Marion,
Moshous Despina,
LefèvreUtile Alain,
Lutun Anne,
Paillard Catherine,
Thomas Caroline,
Jeziorski Eric,
Nizard Philippe,
Taly Valérie,
Emile JeanFrançois,
Donadieu Jean
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14695
Subject(s) - langerhans cell histiocytosis , medicine , biomarker , vemurafenib , chemotherapy , gastroenterology , vinblastine , exact test , oncology , cancer , biology , biochemistry , disease , metastatic melanoma
Summary 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 BRAF V600E ‐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 BRAF V600E 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 BRAF V600E 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 BRAF V600E 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 BRAF V600E load at day 15. Thus, ccf BRAF V600E is a promising biomarker for monitoring the response to therapy for children with RO+ MS LCH or RO− LCH resistant to first‐line chemotherapy.