EIF2AK2 and chordoma: For example, chordoma cells’ high intrinsic expression of ISGs appears to underlie their dependence on the double-strand RNA (dsRNA)-editing enzyme ADAR. It has been proposed that a chronic ISG state confers dependence on ADAR because it poises nucleic acid sensors like PKR to respond to the accumulation of endogenous immunogenic dsRNAs that ADAR normally edits36,37,40.