Circulating cell-free BRAFV600E as a biomarker in children with Langerhans cell histiocytosis.
Sébastien HéritierZofia Hélias-RodzewiczHélène LapillonneNathalie TerronesSonia GarrigouCorinne NormandMohamed-Aziz BarkaouiJean MironGeneviève PlatNathalie AladjidiAnne PagnierAnne DevilleMarion Gillibert-YvertDespina MoshousAlain Lefèvre-UtileAnne LutunCatherine PaillardCaroline ThomasEric JeziorskiPhilippe NizardValérie TalyJean-François EmileJean DonadieuPublished in: British journal of haematology (2017)
The BRAFV600E mutation is reported in half of patients with Langerhans cell histiocytosis (LCH). This study investigated the detection of the BRAFV600E allele in circulating cell-free (ccf) DNA in a paediatric LCH cohort. Children with BRAFV600E -mutated LCH were investigated to detect ccf BRAFV600E 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.
Keyphrases
- cell free
- newly diagnosed
- end stage renal disease
- mass spectrometry
- circulating tumor
- ejection fraction
- multiple sclerosis
- single cell
- ms ms
- cell therapy
- high throughput
- emergency department
- stem cells
- mesenchymal stem cells
- density functional theory
- squamous cell carcinoma
- bone marrow
- circulating tumor cells
- quantum dots
- high resolution
- sensitive detection
- real time pcr
- smoking cessation