Mutation analysis of the KRAS, NRAS, and HRAS gene

Activating mutations of the RAS family of proto-oncogenes, KRAS, NRAS, and HRAS are frequent events in human cancers. The most common mutations occur within the KRAS gene. These are found in 30-40% of colorectal cancers (CRCs)1,2 and 10-30% of non-small cell lung cancers (NSCLCs)4. Most often, these mutations occur at codons 12 and 13, but mutations have also been detected in codons 61, 117, and 146.  Hotspot mutations in KRAS have been associated with poor responsiveness to EGFR monoclonal antibody therapies (cetuximab, panitumumab) in CRCs,3, 7, 8.  For KRAS mutant NSCLCs, some studies have reported decreased sensitivity to EGFR tyrosine kinase inhibitors 5, 6.

Mutations of NRAS and HRAS codons 12, 13, and 61are detectable in a smaller subset of CRCs (~1-6%) and NSCLCs (~1%)9,10.  NRAS mutations have been more frequently detected in melanoma (13-25%) and in thyroid cancers (~6%) where they have been suggested to increase sensitivity to the MEK inhibitor selumetinib11.

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

RAS-NGS Assay Summary (Targeted analysis for 124 cancer hotspot mutations in the KRAS, NRAS and HRAS genes by next generation sequencing.)
(in portable document format (pdf) which requires Adobe® Acrobat® Reader™ to view or print; download latest version free)

  1. Rothberg JM, et al; An integrated semiconducted device enabling non-optical genome sequencing. Nature, 2011 Jul20; 475(7356):348-52
  2. Dancey JE, et al; The genetic basis for cancer treatment decisions. Cell, 2012 Feb 3; 148(3): 409-20. Review
  3. www.mycancergenome.org
  4. www.sanger.ac.uk/genetics/CGP/cosmic/
  5. www.pharmgkb.org/