The landscape of gain and loss of function mutations in melanoma

Major discoveries in melanoma biology have been rapidly translated, allowing cures for some late-stage patients. Despite these advances, incomplete knowledge of genes and pathways that are gained or lost during melanogenesis prohibits cures for many patients.

To identify gain of function and loss of function drivers of melanoma, we established a multi-omics cohort of melanoma patient-derived xenografts (melPDomiX). By linking mutations with gene and protein expression, we characterize gain or loss of function of specific melanoma drivers in treatment refractory tumor models. We use multi-omics integration and structural-context representation to distinguish gain from loss of function variants, revealing new candidate melanoma genes and targets.