As shown in Fig. 3d, the Insm1 promoter was more strongly methylated in the tumors with low insulin and low Insm1. Since promoter hypermethylation is a common mechanism for lowering expression of key tumor suppressor genes, these data suggest that Insm1 expression may not merely correlate with insulinomas, but may actually be a gene that suppresses the formation of nonfunctioning PanNETs. Here, INS is linked to pancreatic insulinoma.