Mutation analysis of the KRAS gene

KRAS somatic mutations are found in 30-40% of colorectal cancers (CRC)1,2.  Most often, these mutations occur at codons 12 and 13, but mutations at other codons (including 61, 117, and 146) have also been detected.  Hotspot KRAS mutations have been associated with poor responsiveness to EGFR monoclonal antibody therapies (cetuximab, panitumumab) in CRCs3, 7, 8.  KRAS mutations are also detected in 10-30% of non-small cell lung carcinomas (NSCLC)4 and studies have reported decreased sensitivity to EGFR tyrosine kinase inhibitors 5, 6. Determining the KRAS status of a newly diagnosed CRC or NSCLC tumor prior to initiating anti-EGFR therapy may be useful in selecting candidates for monoclonal antibody (MAB) therapy and tyrosine kinase inhibitor (TKI) therapy, respectively.  Additionally, testing should be considered for patients who are already on anti-EGFR therapy, but are demonstrating resistance.

To open a printable assay summary in a new window, click the link below.

KRAS-NGS Assay Summary (Targeted analysis for 63 cancer hotspot mutations in the KRAS gene (including codons 12, 13, 61, 117, 146) by next generation sequencing.)
(in portable document format (pdf) which requires Adobe® Acrobat® Reader™ to view or print; download latest version free)

References
  1. Lièvre, A. et al., (2008) J Clin Oncol; 26:374-9
  2. Amado, R. G. et al., (2007) Eur J of Can Supp (5):6
  3. Di Fiore, F. et al., (2007) Br J Cancer; 96:1166-9
  4. Eberhard et al. (2005) J Clin Oncol; 23:5900-9
  5. Han. et al., (2006) Clin Can Res; 12:2538-44
  6. Pao. et al., (2005) PLoS Med; 2:e17
  7. Janakiriman et al. Cancer Res. 2010 Jul 15;70(14):5901-11
  8. Loupakis et al. British Journal of Cancer (2009) 101, 715–721