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KRAS
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Interpretation 399
Tier 1
KRAS
Variants
KRAS G13D
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

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. However, preclinical studies have shown that G13D mutant cell lines have intermediate sensitivity to cetuximab and panitumumab. Results should be interpreted in conjunction with other laboratory and clinical findings.

Citations
  1. Lievre A, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008;26(3):374-9
  2. Amado RG, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008;26(10):1626-34
  3. Pao W, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2(1):e17
  4. Querings S, et al. Benchmarking of mutation diagnostics in clinical lung cancer specimens. PLoS One 2011;6(5):e19601
  5. Janakiraman M, et al. Genomic and biological characterization of exon 4 KRAS mutations in human cancer. Cancer Res 2010;70(14):5901-11
  6. Douillard JY, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013;369(11):1023-34
  7. Kumar SS, et al. KRAS G13D Mutation and Sensitivity to Cetuximab or Panitumumab in a Colorectal Cancer Cell Line Model. Gastrointest Cancer Res 2014;7(1):23-6
Last updated: 2017-03-24 18:09:45 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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