A review of kinase fusions in melanocytic tumors

Translocations resulting in a kinase fusion are well reported in many tumor types and indeed can be defining, particularly in the case of hematopoietic malignancies. The recent reports of multiple protein kinase fusions within melanocytic neoplasms, particularly in those with spitzoid morphology, have heralded a new era of classification of these melanocytic tumors. Seen within approximately half of all spitzoid neoplasms and present within the full spectrum of benign, atypical, and malignant lesions, kinase fusions likely represent an early oncogenic event contributing to cell proliferation and growth. Although the presence of a kinase fusion does not seem to correlate with the biologic potential of a given lesion, documentation of a kinase fusion will likely be important, particularly in the case of spitzoid melanoma, as numerous specific kinase receptor inhibitors have shown promise as therapeutic agents in a subset of cases with kinase fusions. Interrogation of non-spitzoid melanomas for similar kinase fusions as a potential driving oncogenic mechanism has revealed some similarities and some differences. This review will focus on the kinase fusions described to date in spitzoid neoplasms and how subsequent studies have informed current melanoma research.