Thus, sporadic tumours with NF1 mutations are mutually exclusive for mutations in MAPK kinase 1 (MAP2K1) or NRAS. Strongly activating ‘canonical’ mutations in oncogenes (for example G12D or G12V mutations in KRAS) can drive cancer formation on their own and are known to be epistatic in relation to other canonical mutations within the same pathway [164]. Here, NF1 is linked to cancer.