KRAS is a gene that encodes one of the several proteins in the epidermal growth factor receptor (EGFR) signaling pathway that is important in the development and progression of cancer. KRAS can harbor oncogenic mutations that yield a constitutively active protein. Such mutations are found in approximately 30% to 50% of metastatic colorectal tumors and are common in other tumor types. Mutations in the KRAS gene may indicate poor prognosis and poor drug response with therapies targeted to EGFR. The absence of a KRAS mutation predicts a greater likelihood of response to EGFR-targeted therapies and improved survival with such treatment. The relevant KRAS mutation is in one of five codons (12 13, 61, 117 or 146). The presence of KRAS mutations in codon 12, 13 or 61 is associated with a high likelihood of resistance to therapies targeting EGFR. In addition, mutations at codons 117 and 146 may also be associated with reduced response to EGFR-targeted therapies. Results should be interpreted in conjunction with other laboratory and clinical findings. Drug resistance: Panitumumab Cetuximab

KRAS belongs to the RAS family of oncogenes. In lung, KRAS mutations are detected in approximately 20% to 25% of adenocarcinoma and less than 10% of squamous cell carcinoma which demonstrate a minor glandular component. KRAS mutations in NSCLC most often occur in codons 12 or 13 and with a lower frequency in codon 61. Mutations in KRAS are usually mutually exclusive with other oncogenic driver aberrations including EGFR, BRAF, HER2 mutations and ALK and ROS1 rearrangements. Contrary to most other oncogenic driver mutations, KRAS is more often found in smokers and is detected at lower frequency in East Asian patient cohorts. The prognostic as well as predictive role of KRAS mutations continues to be studied. Although various attempts inhibiting KRAS have been made, there is no established therapy specific for this large patient subpopulation. Recommend correlation with other clinical and lab findings.

KRAS belongs to the RAS family of oncogenes. KRAS mutations are detected in approximately 20% to 25% of lung adenocarcinoma. Contrary to most other oncogenic driver mutations, KRAS is more often found in smokers and is detected at lower frequency in East Asian patient cohorts. Mutations in KRAS are usually mutually exclusive with other oncogenic driver aberrations including EGFR, BRAF, HER2 mutations and ALK and ROS1 rearrangements. KRAS mutations in NSCLC most often occur in codons 12 or 13 and with a lower frequency in codon 61. The prognostic as well as predictive role of KRAS mutations continues to be studied. Although various attempts inhibiting KRAS have been made, there is no established therapy specific for this large patient subpopulation.

Pancreatic ductal adenocarcinoma (PDAC) is initiated by oncogenic mutant KRAS, which has been shown to drive pancreatic neoplasia. More than 90% of pancreatic ductal adenocarcinoma samples have a KRAS mutation which may have prognostic, and (with ongoing trials assessing the efficacy of novel KRAS inhibitors) possibly therapeutic implications. However, targeting KRAS directly has been difficult in these tumors.

KRAS is a well known proto-oncogene that belongs to the small GTPase family and functions as a central mediator of downstream growth factor receptor signaling, with a critical role for cell proliferation and survival. Pathogenic mutations in KRAS typically occur in codons 12-13 of exon 2 and codon 61 of exon 3; however, other, non-canonical, pathogenic mutations in KRAS have also been reported in acute myeoid leukemia. KRAS mutations have been described in approximately 3-15% of acute myeloid leukemia, 8-20% of chronic myelomonocytic leukemia, 14% of juvenile myelomonocytic leukemia, 8% of blastic plasmacytoid dendritic cell neoplasm 4% of patients with myelodysplastic syndrome, 2% of primary myelofibrosis, 12% of B cell acute lymphoblastic leukemia (often associated with MLL rearrangement) and 1-2% of T cell acute lymphoblastic leukemia. Investigation into the targetability of this pathway in leukemia has been attempted in some disease models.

KRAS is a gene that encodes one of the several proteins in the epidermal growth factor receptor (EGFR) signaling pathway that is important in the development and progression of cancer. KRAS can harbor oncogenic mutations that yield a constitutively active protein. KRAS mutations are frequent in low-grade mucinous tumors of appendiceal origin and pseudomyxoma peritonei (43-100%) where mutations commonly occur in codon 12 or 13, with G12D and G12V being the most common. However, appendiceal adenocarcinoma cases with goblet cell features usually lack KRAS mutations. Mutations in the KRAS gene may indicate poor prognosis and drug response with therapies targeted to EGFR in some settings. However, this should be interpreted in conjunction with other laboratory and clinical findings.

KRAS is a gene that encodes one of the several proteins in the epidermal growth factor receptor (EGFR) signaling pathway that is important in the development and progression of cancer. KRAS can harbor oncogenic mutations that yield a constitutively active protein. Such mutations are found in approximately 30% to 60% of small intestine adenocarcinomas and are common in other tumor types. The relevant KRAS mutation is in one of five codons (12 13, 61, 117 or 146). KRAS mutations in small intestine tumors are associated with higher pT classification and more frequent pancreatic invasion. The effect of KRAS mutations on drug therapy has not been well established in the literature, however it has been extensively studied in colorectal adenocarcinoma. Mutations in the KRAS gene may indicate poor prognosis and poor drug response with therapies targeted to EGFR in colon cancer, and the absence of a KRAS mutation predicts a greater likelihood of response to EGFR-targeted therapies and improved survival with such treatment. The presence of KRAS mutations in codon 12, 13 or 61 is associated with a high likelihood of resistance to therapies targeting EGFR in colon cancer. In addition, mutations at codons 117 and 146 may also be associated with reduced response to EGFR-targeted therapies in colon cancer. Results should be interpreted in conjunction with other laboratory and clinical findings.

KRAS is a gene that encodes one of the several proteins in the epidermal growth factor receptor (EGFR) signaling pathway that is important in the development and progression of cancer. KRAS can harbor oncogenic mutations that yield a constitutively active protein. KRAS mutations are common in both extrahepatic (40-49%) and intrahepatic (24-27%) cholangiocarcinomas. Mutations in the KRAS gene may indicate poor prognosis and drug response with therapies targeted to EGFR in some settings. Of note, RAS mutations sensitize tumors to MEK inhibitors. However, this should be interpreted in conjunction with other laboratory and clinical findings.

RAS mutations (HRAS, NRAS and KRAS) are found in all epithelial thyroid malignancies. The frequency of KRAS mutations in thyroid carcinomas is 2-3%. Overall, RAS mutations are identified in 10--20% of papillary carcinomas (follicular variant), 40--50% of follicular carcinomas and 20--40% of poorly differentiated and anaplastic carcinomas. Of note, RAS point mutations are mutually exclusive with other thyroid mutations such as BRAF, RET/PTC, or TRK rearrangements in papillary thyroid cancers. In follicular carcinomas, RAS mutations are mutually exclusive with PAX8-PPARG rearrangements. RAS mutations have also been associated with more aggressive disease and distant metastasis. The therapeutic implications of RAS mutations in thyroid cancer are unknown at this time.