Despite their common clinical and pathological features and RNA-seq profiles10, insulinomas contain variants in a broad range of epigenetic modifying enzymes, exemplified by Trithorax, Polycomb, and related members such as MEN1, KDM6A, MLL3/KMT2C, YY1, KDM5B, and SMARCC1. As an example, inactivating mutations in MEN1, an H3K4me3 methylase and a canonical member of the Trithorax family, are common in sporadic and familial insulinomas. The gene discussed is SMARCC1; the disease is pancreatic insulinoma.