KRAS Testing

Medical Solutions™ is now offering KRAS mutation testing on paraffin-embedded clinical material. The test includes a histolopathology review of the sample to ensure tumour tissue is present. The assay uses the DxS Ltd Therascreen™ KRAS Mutation Testing kit, which is designed to detect the 7 most common activating mutations of the KRAS gene.

Recent studies in non small cell lung cancer and colorectal cancer show that activating mutations of the gene encoding the signalling molecule KRAS, are likely to give rise to resistance to:

  • small molecule drugs e.g. (erlotinib; gefitinib) and
  • antibody treatments e.g. (cetuximab, panitumumab) targeted at the Epidermal Growth Factor Receptor (EGFR)

This is because KRAS lies downstream in the EGFR signalling pathway and therefore, if it is continuously active based upon the presence of a mutation in the KRAS gene, inhibition of EGFR by the drugs listed above will be ineffective.

Testing for KRAS activating mutations may therefore offer further refinement to the treatment decision-making process, separating patients according to likely response to these agents. Serial sections are cut from the paraffin block and DNA extracted. The DNA is then amplified using a combination of Scorpions™ and ARMS™ (allele specific PCR) technologies to detect the 7 most common nucleotide substitutions, all present in codons 12 and 13 of the KRAS gene. The assay is sensitive to 1% of mutant DNA in a background of wild type genomic DNA.

A positive result in this test indicates the presence of an activating mutation in the KRAS gene, and suggests that this patient is unlikely to respond favourably to treatment with small molecule or antibody treatment targeted at EGFR.

References

  1. Mitsudomi T and Yatabe Y (2007) Cancer Sci 98:1817-24
  2. Massarelli E et al (2007) Clin Cancer Res 13:2890-96
  3. Finocchiaro G et al (2007) J Clin Oncol, ASCO Annual Meeting Proceedings 25 (18S):4021