Testing for BRAF fusions in patients with advanced BRAF/NRAS/KIT wild-type melanomas permits to identify patients who could benefit of anti-MEK targeted therapy

• Published in: Journal of clinical pathology Vol. 73; no. 2; pp. 116 - 119
• Main Authors: Le Flahec, Glen, Briolais, Manon, Guibourg, Briac, Lemasson, Gilles, Grippari, Jean-Luc, Ledé, Francoise, Marcorelles, Pascale, Uguen, Arnaud
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and Association of Clinical Pathologists 01.02.2020; BMJ Publishing Group LTD
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Apoptosis; Biomarkers, Tumor - genetics; Brain cancer; Female; fluorescent; Gene Fusion; GTP Phosphohydrolases - genetics; Humans; hybridization; Immunotherapy; In Situ Hybridization, Fluorescence; Male; Melanoma; Melanoma - drug therapy; Melanoma - enzymology; Melanoma - genetics; Membrane Proteins - genetics; Metastasis; Middle Aged; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinase Kinases - metabolism; Molecular Targeted Therapy; Mutation; Patient Selection; Patients; Precision Medicine; Predictive Value of Tests; Protein Kinase Inhibitors - therapeutic use; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins c-kit - genetics; Short report; Skin Neoplasms - drug therapy; Skin Neoplasms - enzymology; Skin Neoplasms - genetics; Tumors; Germany; melanoma; fluorescentin situhybridization; BRAF; gene fusion
• ISSN: 0021-9746; 1472-4146; 1472-4146
• DOI: 10.1136/jclinpath-2019-206026

Beyond targeted therapy for patients with BRAF-mutated melanomas and immunotherapy in patients lacking BRAF mutations, anti-MEK therapy has been proposed in patients with advanced melanomas harbouring BRAF fusions. BRAF fusions diagnosis in patients with advanced melanomas is the subject of the present study. Using BRAF fluorescent in situ hybridisation (FISH), we searched for BRAF fusions in 74 samples of 66 patients with advanced BRAF/NRAS/KIT wild-type melanomas. We identified 2/66 (3%) patients with BRAF fusions in a brain metastasis of one patient and in a lymph node metastasis and in a cutaneous metastasis for the second patient with 90%–95% of tumour nuclei containing isolated 3′-BRAF FISH signals. As a result, we conclude that BRAF FISH in patients with advanced BRAF/NRAS/KIT wild-type melanomas is a valuable and easy-to-perform test to diagnose BRAF fusions and to identify patients who could benefit of anti-MEK targeted therapy.