A30: SF3B1 and EIF1AX mutations in Uveal Melanoma
1Erasmus MC, Department of Clinical Genetics, Rotterdam, The Netherlands,2Erasmus MC, Department of Ophthalmology, Rotterdam, The Netherlands,3Erasmus MC, Department of Pathology, Rotterdam, The Netherlands,4The Rotterdam Eye Hospital, Rotterdam, The Netherlands
The genetic framework of uveal melanoma (UM) is slowly being unraveled with the discovery of somatic mutations in GNAQ, GNA11, BAP1, EIF1AX and SF3B1. Metastasis is the main cause of UM-related death, and therefore a better understanding and adequate classification models on basis of these mutations and chromosomal anomalies can help to identify high-risk patients.
We investigated EIF1AX and SF3B1 mutations in 130 UM patients with Sanger sequencing or whole exome sequencing (30 samples). The GNAQ and GNA11 mutation status and the presence of BAP1 expression in the tumor specimen were also investigated.
We confirmed that EIF1AX mutations have a protective effect since tumors with these mutations rarely metastasize (disease-free survival (DFS) mutant versus wildtype respectively 190.1 and 103.1 months, P <0.01). Strikingly, we found that concurrent disomy 3 and SF3B1 mutations in tumors significantly also increases the metastatic risk of UM patients (DFS mutant vs wildtype respectively 141.3 and 169.2 months, P = 0.05).
These results indicate that SF3B1 is not a protective factor in favorable disomy 3 UM as is currently assumed, but that these UM patients will develop late metastases after a prolonged DFS of >7 years.