Data analysis of patients with lung adenocarcinoma and melanoma show that of all RASGAPs only inactivating mutations in NF1 tend to occur in a mutually exclusive manner with activating hotspot mutations in KRAS, NRAS and BRAF. This suggests that the loss of NF1 is sufficient to drive aberrant activity of the RAS-MAPK signaling pathway in the absence of other mutations in the RAS signaling pathway. Here, NRAS is linked to lung adenocarcinoma.