Similar to other malignancies, TCGA network efforts identified the detailed genomic
picture of skin melanoma, laying down the basis of molecular classification. On the
other hand, genome-wide association studies discovered the genetic background of the
hereditary melanomas and the susceptibility genes. These genetic studies helped to
fine-tune the differential diagnostics of malignant melanocytic lesions, using either
FISH tests or the myPath gene expression signature. Although the original genomic
studies on skin melanoma were mostly based on primary tumors, data started to accumulate
on the genetic diversity of the progressing disease. The prognostication of skin melanoma
is still based on staging but can be completed with gene expression analysis (DecisionDx).
Meanwhile, this genetic knowledge base of skin melanoma did not turn to the expected
wide array of target therapies, except the BRAF inhibitors. The major breakthrough
of melanoma therapy was the introduction of immune checkpoint inhibitors, which showed
outstanding efficacy in skin melanoma, probably due to their high immunogenicity.
Unfortunately, beyond BRAF, KIT mutations and tumor mutation burden, no clinically
validated predictive markers exist in melanoma, although several promising biomarkers
have been described, such as the expression of immune-related genes or mutations in
the IFN-signaling pathway. After the initial success of either target or immunotherapies,
sooner or later, relapses occur in the majority of patients, due to various induced
genetic alterations, the diagnosis of which could be developed to novel predictive
genetic markers.
