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KRAS
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Interpretation 152
Tier 1
KRAS
Variants
KRAS G12A
KRAS G12V
KRAS G12D
KRAS G12C
KRAS G12S
KRAS G12R
KRAS G13C
KRAS G13S
KRAS G13R
KRAS Q61H
KRAS Q61L
KRAS Q61K
KRAS Q61R
KRAS A146T
KRAS A146V
KRAS A146P
KRAS A11V
KRAS codon(s) 12, 13, 61, 117, 146 any
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Carcinoma
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. 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

Citations
  1. Janakiraman M, et al. Genomic and biological characterization of exon 4 KRAS mutations in human cancer. Cancer Res 2010;70(14):5901-11
  2. Douillard JY, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013;369(11):1023-34
  3. 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
  4. 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
  5. Pao W, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2(1):e17
  6. Querings S, et al. Benchmarking of mutation diagnostics in clinical lung cancer specimens. PLoS One 2011;6(5):e19601
  7. Bokemeyer C, et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol 2011;22(7):1535-46
  8. De Roock W, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 2010;11(8):753-62
Last updated: 2020-01-25 17:53:49 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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