MMR deficiency alone increases the mutation rate, represents an advantageous genotype and could be fixed during tumor development; however, after a clonal expansion of dMMR, POLD1 exonuclease mutations will further increase the mutation rate by an order of magnitude (Fig. 3G) and thus, should also cause positive selection. This evidence concerns the gene MRC1 and hyperinsulinemic hypoglycemia, familial, 4.