Uveal melanoma cell lines are representative for their tumour, except cell lines Mel285 and Mel290: the odd two out

Purpose: In uveal melanoma (UM) research, several cell lines are used in preclinical studies. Because Mel285 and Mel290 do not harbour typical GNAQ or GNA11 hotspot mutations, we aimed at better classifying them and understanding if we could find genetic causes to explain their protein and mRNA expression profiles. Methods: We studied protein and mRNA expression in 14 UM cell lines and determined the presence of Single Nucleotide Variants and small Insertions and Deletions with next generation sequencing and copy number alterations (CNAs) with a single nucleotide polymorphism array. The lists of differentially expressed proteins and genes were merged, and shared lists were created, keeping only the terms with concordant mRNA and protein expression. Enrichment analysis and Gene Set Enrichment Analysis were performed on the shared lists. Results: Mel285 and Mel290 are distinct from the GNA-mutated cell lines and have downregulation of melanosome-related markers. Mel285 and Mel290 lack typical UM mutations but harbour putatively-deleterious variants in four genes each (Mel285: CTNNB1, PPP1R10, LIMCH1, APC; Mel290: ARID1A, PPP1R10, SPG11, RNF43). The upregulated terms in Mel285 and Mel290 did not point to a convincing alternative origin. Mel285 has several CNAs, among which loss of 1p, 3p, partial 3q, 6 and partial 8p, while Mel290 shows 1p loss and chromosome 6 loss. Conclusion: While Mel285 and Mel290 have some CNAs that resemble those in UM, multi-omics analyses show that they belong to a separate group compared to the other analysed UM cell lines. Therefore, they may not be representative models to test potential therapeutic targets for UM.