SF3B1 mutations are associated with alternative splicing in uveal melanoma
Menée initialement sur 12 échantillons tumoraux prélevés sur des patients atteints d'un mélanome primitif de l'uvée, puis sur 105 échantillons complémentaires, cette étude identifie des mutations du gène SF3B1 en association avec un épissage alternatif différentiel des gènes ABCC5 et UQCC
Uveal melanoma, the most common eye malignancy causes severe visual morbidity and is fatal in about 50% of patients. Primary uveal melanoma can be cured by surgery or radiotherapy, but the metastatic disease is treatment refractory. To understand comprehensively uveal melanoma genetics, we performed SNP arrays and whole genome sequencing on 12 primary uveal melanomas. We observed only ~2000 predicted somatic single nucleotide variants per tumor and low levels of aneuploidy. We did not observe an ultraviolet radiation DNA-damage signature, but identified SF3B1 mutations in three samples and a further 15 mutations in an extension cohort of 105 samples. SF3B1 mutations were associated with good prognosis and were rarely coincident with BAP1 mutations. SF3B1 encodes a component of the spliceosome and RNA sequencing revealed that SF3B1 mutations were associated with differential alternative splicing of protein coding genes including ABCC5 and UQCC, and of the long non-coding RNA (lncRNA) CRNDE.
Cancer Discovery 2013