ARNT and melanoma: Since we did not find any recurrent mutation that may support constitutive activation of AhR in the TCGA melanoma cohort (cBioPortal: http://www.cbioportal.org/index.do), we hypothesized that endogenous α-ligands produced in drug-resistant cells may result in sustained activation of the AhR/ARNT pathway (Fig. 5b) and thereby promote the α-signature.