Loss of ten-eleven translocation 2 (TET2) facilitates aggressive behaviour in cutaneous melanoma by inducing peroxisome proliferator-activated receptor-γ coactivator 1α expression and oxidative phosphorylation

Loss of TET2 promotes activation of PGC-1α/OXPHOS in melanoma, driving metabolic reprogramming that supports tumour progression and resistance to MAPK inhibition in a subset of tumours. Importantly, this phenotype renders TET2-deficient melanomas selectively vulnerable to OXPHOS inhibition, identifying an actionable therapeutic opportunity. These findings establish an epigenetic-metabolic axis as a critical determinant of melanoma aggressiveness and highlight TET2/5-hmC as a potential biomarker and a targetable pathway.