Expression of these TFs, including GATA3, PHOX2A, PHOX2B, HAND2/TWIST1, TBX2, and ISL1, is essential in MYCN-amplified NB (11, 13), suggesting that an oncogenic feed-forward interaction among MYCN, tissue-specific enhancers, and additional TFs constitutes a core regulatory circuitry that underlies maintenance of lineage-related NB gene expression programs. This evidence concerns the gene HAND2 and neuroblastoma.