Systematic application of NGS has led to the discovery of a myriad of somatic mutations. One important class of genes affected by mutations in myeloid neoplasia (MN) is involved in epigenetic regulation either directly by modifying DNA or by enzymes modifying histones such as histone methyltranferases and demethylases (e.g., EZH2, MLL, UTX). This work focuses on mutations of EP300, a histone acetyl transferase. EP300(22q13.2) encodes the adenovirus E1A associated cellular p300 transcriptional co-activator protein with lysine acetyltransferase activity as does its paralog CBP (16p13.3). Ablation of EP300in mice results in embryonic lethality. Heterozygous germline EP300mutations were described in Rubinstein-Taybi syndrome (RBTS), a congenital neurodevelopmental disorder characterized by facial dysmorphology, distal limb abnormalities and mental retardation. In addition, RTBS patients appear to have a predisposition for childhood malignancies. Somatic EP300mutations have been found in solid tumors and lymphoid neoplasia but have been less studied in MN.