Laboratory methods for KRAS mutation analysis

Abstract

The determination of KRAS mutational status from tumor samples has become an important tool for patient management in colorectal and non-small-cell lung cancers. Mutations in critical areas of the gene, such as codons 12 and 13, are a negative predictor of response to anti-EGF receptor antibodies in colorectal cancer, and similarly are indicators of resistance to small-molecule tyrosine kinase inhibitors in non-small-cell lung cancer patients. A variety of laboratory methods have been developed to assess mutation status in key regions of the KRAS gene. Many of these methods, including allele-specific PCR, real-time PCR methods with melt–curve analysis, and nucleic acid sequencing techniques, provide the appropriate analytical performance to address tissue heterogeneity in tumor samples. The pathologist plays a key role in this process because assessment of morphological features of the tumor is important prior to molecular analysis. This article provides a summary of the performance characteristics of various molecular testing methods and addresses other key aspects of testing necessary to provide relevant information to help determine appropriate therapy choices.

Keywords::

• cetuximab
• colorectal cancer
• KRAS gene
• mutation analysis
• panitumumab

Financial & competing interests disclosure

Steven M Anderson is an employee of Laboratory Corporation of America^® (NC, USA). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.