Additional investigation will be required to determine whether specific HIF2α target genes critical for tumor growth require both ARNT and BMAL1 to reach an expression threshold that is needed to support tumor formation or if loss of distinct genes driven by ARNT-HIF2α or by BMAL1-HIF2α contributes to growth impairment upon depletion of each heterodimer. Here, EPAS1 is linked to neoplasm.