Our novel framework to study the role of NF1 in tumorigenesis integrates the concept of NF1 as a tumor predisposition gene, knowledge derived from the Krox20-Cre; Nf1f/− mouse model14,66, while at the same time explaining why NF1 patients develop mostly benign tumors instead of developing the cancer types with high NF1 mutation rates as seen in the general population. Here, NF1 is linked to cancer.