Histone-modifying genes, including lysine methyltransferase 2D (KMT2D), lysine methyltransferase 2C (KMT2C), CREB-binding protein (CREBBP), and E1A-binding protein p300 (EP300), have been shown to be frequently altered in SCLC [42], and mutations of these genes are largely mutually exclusive in GEP-NEC [11, 56, 58] (Table 3 and Fig. 1). This evidence concerns the gene KMT2D and neuroendocrine carcinoma.