BRAF Mutation Correlates With High-Risk Langerhans Cell Histiocytosis and Increased Resistance to First-Line Therapy - Centre de recherche en cancérologie Nantes-Angers Unité Mixte de Recherche 892 Inserm - 6299 CNRS Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Oncology Année : 2016

BRAF Mutation Correlates With High-Risk Langerhans Cell Histiocytosis and Increased Resistance to First-Line Therapy

1 CHU Trousseau [APHP]
2 BECCOH - Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie
3 Hôpital Trousseau
4 CHU Nantes - Centre Hospitalier Universitaire de Nantes
5 UPD5 - Université Paris Descartes - Paris 5
6 Hôpital Haut-Lévêque [CHU Bordeaux]
7 IMJ - Institut de Mathématiques de Jussieu
8 EA_3102 - Pathologie pédiatrique
9 Centre Léon Bérard [Lyon]
10 HCL - Hospices Civils de Lyon
11 INM - Institut des Neurosciences de Montpellier
12 Developpement Normal et Pathologique du Système Immunitaire
13 Service d'hématologie pédiatrique-oncologie
14 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
15 Institut d’Hémato-Oncologie Pédiatrique
16 IGMM - Institut de Génétique Moléculaire de Montpellier
17 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
18 Hôpital Pellegrin
19 HUDERF - Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique]
20 Institut Curie [Paris]
21 Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM]
22 Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy]
23 Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy]
24 UPMC - Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie
25 CHU Nice - Centre Hospitalier Universitaire de Nice
26 Hôpital de la Tronche
27 CHU Amiens-Picardie
28 CHU Trousseau [Tours]
29 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
30 CHU Pitié-Salpêtrière [AP-HP]
31 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers
32 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
33 Service d'hématologie et immunologie pédiatrique
34 Service de médecine de l'enfant et de l'adolescent [CHU Rennes]
35 Service de dermatologie [CHU Necker]
36 CHU Tenon [AP-HP]
37 MEPPOT - U1147 - Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique
38 Memorial Sloane Kettering Cancer Center [New York]
Anne Moreau
  • Fonction : Auteur
  • PersonId : 829226
Valérie Rigau
  • Fonction : Auteur
  • PersonId : 913072
Jean Miron
  • Fonction : Auteur
Anne Lutun
  • Fonction : Auteur
Christine Bodemer
Roger Lacave
  • Fonction : Auteur

Résumé

PURPOSE: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF(V600E) mutation occurs frequently, but clinical significance remains to be determined. PATIENTS AND METHODS: BRAF(V600E) mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae. RESULTS: Among 315 patients with successfully determined BRAF status, 173 (54.6%) carried a BRAF(V600E) mutation. Patients with BRAF(V600E) manifested more severe disease than did those with wild-type BRAF. Patients with BRAF(V600E) comprised 87.8% of patients (43 of 49) with multisystem LCH with risk organ involvement (liver, spleen, hematology), 68.6% of patients (35 of 51) with multisystem LCH without risk organ involvement, 43.9% of patients (86 of 196) with single-system LCH, and 42.1% of patients (8 of 19) with lung-involved LCH (P < .001). BRAF(V600E) mutation was also associated with organ involvement that could lead to permanent, irreversible damage, such as neurologic (75%) and pituitary (72.9%) injuries. Compared with patients with wild-type BRAF, patients with BRAF(V600E) more commonly displayed resistance to combined vinblastine and corticosteroid therapy (21.9% v 3.3%; P = .001), showed a higher reactivation rate (5-year reactivation rate, 42.8% v 28.1%; P = .006), and had more permanent, long-term consequences from disease or treatment (27.9% v 12.6%; P = .001). CONCLUSION: In children with LCH, BRAF(V600E) mutation was associated with high-risk features, permanent injury, and poor short-term response to chemotherapy. Further population-based studies should be undertaken to confirm our observations and to assess the impact of BRAF inhibitors for this subgroup of patients who may benefit from targeted therapy.
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Dates et versions

inserm-02304878 , version 1 (03-10-2019)

Identifiants

Citer

Sébastien Heritier, Jean-François Emile, Mohamed-Aziz Barkaoui, Caroline Thomas, Sylvie Fraitag, et al.. BRAF Mutation Correlates With High-Risk Langerhans Cell Histiocytosis and Increased Resistance to First-Line Therapy. Journal of Clinical Oncology, 2016, 34 (25), pp.3023-3030. ⟨10.1200/JCO.2015.65.9508⟩. ⟨inserm-02304878⟩
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