Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma

Abstract

Approximately 25% of all uveal melanoma (UM) contain driver mutations in the gene encoding the spliceosome factor <i>SF3B1</i>, and whilst patients with such <i>SF3B1</i> mutations generally have an intermediate risk on developing metastatic disease, a third of these patients develop early metastasis within 5 years after diagnosis. We therefore investigated whether clinical and/or genetic variables could be indicative of short progression-free survival (PFS < 60 months) or long PFS (PFS ≥ 60 months) for <i>SF3B1</i>-mutated (<i>SF3B1</i>^mut) UM patients. We collected 146 <i>SF3B1</i>^mut UM from our Rotterdam Ocular Melanoma Studygroup (ROMS) database and external published datasets. After stratification of all <i>SF3B1</i>^mut UM using short PFS vs. long PFS, only largest tumor diameter (LTD) was significantly larger (mean: 17.7 mm (±2.8 SD) in the short PFS <i>SF3B1</i>^mut group vs. the long PFS group (mean: 14.7 (±3.7 SD, <i>p</i> = 0.001). Combined ROMS and The Cancer Genome Atlas (TCGA) transcriptomic data were evaluated, and we identified <i>SF3B1</i>^mut-specific canonical transcripts (e.g., a low expression of <i>ABHD6</i> indicative for early-onset metastatic disease) or distinct expression of <i>SF3B1</i>^mut UM aberrant transcripts, indicative of early- or late-onset or no metastatic <i>SF3B1</i>^mut UM.