More importantly, in the insulinoma context, the observation that these PDX1 binding sites are hypermethylated and less accessible in insulinomas than in beta cells, and the failure of PDX1 to bind to these same sites in insulinoma cells (Supplementary Fig. 10), strongly suggests that alternate, non-PDX1 mechanisms, including sites in the hypomethylated purple region, mediate INS, and possibly INS-IGF2, expression in insulinomas. Here, IGF2 is linked to pancreatic insulinoma.