Spliceosome Mutations in Uveal Melanoma
Josephine Q.N. Nguyen, Wojtek Drabarek, Serdar Yavuzyiğitoğlu, Eva Medico Salsench, Robert M. Verdijk, Nicole C. Naus, Annelies de Klein, Emine Kılıç, Erwin Brosens
Abstract
Uveal melanoma (UM) is the most common primary intraocular malignancy of the eye. It has a high metastatic potential and mainly spreads to the liver. Genetics play a vital role in tumor classification and prognostication of UM metastatic disease. One of the driver genes mutated in metastasized UM is subunit 1 of splicing factor 3b (SF3B1), a component of the spliceosome complex. Recurrent mutations in components of the spliceosome complex are observed in UM and other malignancies, suggesting an important role in tumorigenesis. SF3B1 is the most common mutated spliceosome gene and in UM it is associated with late-onset metastasis. This review summarizes the genetic and epigenetic insights of spliceosome mutations in UM. They form a distinct subgroup of UM and have similarities with other spliceosome mutated malignancies.