KRAS

Mutations in the KRAS gene are found in 15% of cancers, including 92% of pancreatic cancers, 30-50% of colorectal cancers, 10-40% of ovarian cancers, 28% of biliary tract cancers, 15-25% of lung cancers, 15% of endometrial cancers, 6% of stomach cancers, 2% of thyroid cancers, 5% of acute myeloid leukemias, and 2% of breast cancers. In the majority of cases, these mutations are missense mutations which introduce an amino acid substitution at position 12, 13, or 61. The result of these mutations is constitutive activation of KRAS signaling pathways. Recent studies showed that mutations in the KRAS gene are associated with a poor prognosis and predictive of limited clinical response to cancer therapies targeted to the EGFR/KRAS pathway. KRAS mutations predict resistance to EGFR inhibitors in lung cancer and colorectal cancer.