Purpose
Rationale: In uveal melanoma (UM) non‐random chromosomal aberrations occur and correspond to patients’ prognosis. Mutations in UM specific genes, such as BAP1, SF3B1 and EIF1AX are also used to predict survival. Aim of this study is to identify these mutations corresponding to a specific chromosomal signature in UM.
Methods
For 277 UM patients SNP array data (n = 214) and/or conventional karyotyping (n = 119) of the tumor was available. The mutational status was known in 189 patients. Based on the mutational status, SNP array and conventional karyotyping data was analyzed for recurring copy number variations (CNVs) and structural variants (SVs). Hierarchal clustering of the SNP array data was performed to construct clusters. These clusters were correlated to the mutational status.
Results
BAP1, SF3B1 and EIF1AX‐mutated UMs display specific chromosomal patters with recurring CNVs. Both BAP1‐mutated and SF3B1‐mutated UMs are characterized by specific chromosome anomalies and SF3B1 mutated tumors were characterized by multiple (>3) SVs of the genome. EIF1AX‐mutated UM were characterized by only chromosome 6p gain without additional CNVs. Hierarchal clustering of the SNP array data revealed five clusters of which two clusters predicted BAP1 mutations, one cluster SF3B1 mutations, one cluster EIF1AX mutations or wildtype UM and one cluster predicted SF3B1 mutations, EIF1AX mutations or wildtype.
Conclusion
UMs with either BAP1, SF3B1 or EIF1AX mutations display a mutation‐specific chromosomal pattern. Based on the chromosomal patterns the genetic mutation in UM can be predicted.