Neuroblastoma derives from embryonic neural crest cells, and in NB tumors that harbor amplification of the proto-oncogene MYCN, a transcriptional core regulatory circuitry (CRC) that includes MYCN, HAND2, ISL1, PHOX2B, GATA3, and TBX2 promotes tumorigenesis (44). The gene discussed is PHOX2B; the disease is neuroblastoma.