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KRAS Gene Mutation Testing

KRAS Gene Mutation Testing

In different cancer types, in particular those of colorectum and lung, certain subsets of patients have been shown to benefit from anti-EGFR therapies; however a significant proportion show no benefit from these agents.

The KRAS gene encodes a protein that plays a key role in transmitting the original signal from EGFR downstream to activate important cell functions, in particular proliferation and survival.

Acquired mutations of this gene commonly occur in pancreatic, colorectal and lung tumours. These mutations are activating, leading to uncontrolled signalling. They occur primarily in one small region of the gene and make tumours resistant to anti-EGFR therapies. Patients with such mutations in their tumours are therefore considered unlikely to benefit from anti-EGFR therapies. Current guidelines in the US and Europe suggest that all patients being considered for such therapies should be tested for KRAS mutations.

Source BioSceince offer KRAS mutation testing suitable for archival FFPE tissue samples:

  • For routine samples,  pyrosequencing  is performed on the Qiagen/Biotage PyroMark™ system, which detects activating mutations in codons 12, 13 and 61 of the KRAS gene

These mutations are associated with resistance to the anti-EGFR monoclonal antibody therapeutics cetuximab (Erbitux™) and panitumumab (Vectibix™), and the small molecule inhibitors of EGFR gefitinib (Iressa™) and erlotinib (Tarceva™). The results of mutation tests are reported as positive or negative for the presence of a particular mutation, along with additional information about relative frequencies of particular mutations in colorectal and lung tumours.

Further information:

Mutations:

Mutations are identified against the NCBI reference sequence (RefSeq ID : NM_033360)

Amino acid change

Nucleic acid change

p.Gly12Asp

c.35G>A

p.Gly12Val

c.35G>T

p.Gly12Cys

c.34G>T

p.Gly12Ala

c.35G>C

p.Gly12Ser

c.34G>A

p.Gly12Arg

c.34G>C

p.Gly13Asp

c.38G>A

p.Gln61His

c.183A>C

p.Gln61His

c.183A>T


Mutations are reported as per the internationally recognised Human Genome Variation Society format where p.Gly12Asp refers to an amino acid change at codon 12 from Gly to Asp and c.35G>A refers to a nucleic acid change at position 35 from G to A.

Source BioScience provide the highest quality reporting and service standards with rapid turnaround times of <3 days, with reflex test (eg NRAS) turned around in an additional 2 days, providing a comprenhensive and analytically robust service to the clinician. 

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References:
 

National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology for Colon and Rectal Cancer. Published online November 2008. http://www.nccn.org/about/news/newsinfo.asp?NewsID=194  

van Krieken et al. (2008) KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchows Arch 453:417

For further information and prices please contact us or call +44 (0)115 973 9012  

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