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

J Clin Pathol. 2020 Feb;73(2):116-119. doi: 10.1136/jclinpath-2019-206026. Epub 2019 Sep 10.

Abstract

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.

Keywords: BRAF; fluorescentin situhybridization; gene fusion; melanoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Female
  • GTP Phosphohydrolases / genetics*
  • Gene Fusion*
  • Humans
  • In Situ Hybridization, Fluorescence*
  • Male
  • Melanoma / drug therapy
  • Melanoma / enzymology
  • Melanoma / genetics*
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Molecular Targeted Therapy
  • Patient Selection
  • Precision Medicine
  • Predictive Value of Tests
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins c-kit / genetics*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / genetics*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Membrane Proteins
  • Protein Kinase Inhibitors
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinase Kinases
  • GTP Phosphohydrolases
  • NRAS protein, human