Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Academic Article uri icon

Overview

abstract

  • Spitzoid neoplasms are a group of melanocytic tumours with distinctive histopathological features. They include benign tumours (Spitz naevi), malignant tumours (spitzoid melanomas) and tumours with borderline histopathological features and uncertain clinical outcome (atypical Spitz tumours). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbour kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%) and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signalling pathways, are tumourigenic and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz naevi, 56% of atypical Spitz tumours and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signalling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanomas.

publication date

  • January 1, 2014

Research

keywords

  • Melanoma
  • Nevus, Epithelioid and Spindle Cell
  • Oncogene Proteins, Fusion
  • Protein Kinases
  • Skin Neoplasms

Identity

PubMed Central ID

  • PMC4084638

Scopus Document Identifier

  • 84892882633

Digital Object Identifier (DOI)

  • 10.1038/ncomms4116

PubMed ID

  • 24445538

Additional Document Info

volume

  • 5