These can be attributed to mutations in the POLE gene that cause DNA polymerase ε deficiency [10]: we find an increased overall mutation rate, a very high proportion of T[C >A]T and T[C >T]G mutations and a high contribution of COSMIC signature 10 in six out of 42 colon cancer samples [11]. This evidence concerns the gene POLE and hyperinsulinemic hypoglycemia, familial, 4.