This notion is supported by the finding that the most active super-enhancers in neuroblastoma cell lines include the enhancers for transcription factors (PHOX2B, HAND2, GATA3) that are essential for the normal development of sympathoadrenal cells and that form a core regulatory circuitry (CRC) in neuroblastoma [79,80,81,82]. The gene discussed is HAND2; the disease is neuroblastoma.