IDH mutations may define a unique subset of melanoma patients who are eligible for IDH1 targeted therapies or combined therapies, such as MEK inhibitors when there is co-existing NRAS mutations, or immunotherapy.
The analysis of protein and RNA expression levels from the Human Protein Atlas showed that IDH2, which was an essential gene in the melanoma models, but not IDH1 protein, was detected in normal skin cell types and melanoma.
Mutations in the metabolic enzymes isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are frequently found in glioma, acute myeloid leukemia (AML), melanoma, thyroid cancer, and chondrosarcoma patients.
Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy.