The Laboratory Assessment of KRAS Mutation Status in Colorectal Cancer

Christos S. Karapetis, Lesley E. Snell

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)

Abstract

Monoclonal antibodies that bind to the epidermal growth factor receptor (EGFR), particularly cetuximab and panitumumab, can improve overall survival and prolong progression-free survival in patients with advanced colorectal cancer. However, approximately 40% of patients will have tumours that have KRAS mutations, and these patients do not obtain benefit from such therapy. Such patients can be excluded from receiving a treatment that may otherwise cause toxicity. The majority of mutations occur in exon 2, at the first and second nucleotide positions of codons 12 and 13 of the gene. Commercial KRAS test kits target all or the most common of these mutations. Formalin-fixed, paraffin-embedded tissue is usually supplied to the molecular biology laboratory for DNA extraction and subsequent examination by the polymerase chain reaction (PCR). An accurate, reliable, rapid, and cost-effective method to determine the KRAS mutation status of tumors is of crucial importance as clinicians start to apply this information in optimal treatment selection. Laboratory standardization and quality control initiatives are required processes in the adoption of new KRAS detection procedures. At the present time, there is no universally accepted gold standard technique for KRAS mutation evaluation. Several KRAS mutation detection methodologies, including PCR-single strand conformational polymorphism (SSCP), high-resolution melting (HRM), Sanger sequencing, pyrosequencing, the DxS kit, and the TIB MolBiol kits, have been compared and show a high degree of concordance. There are advantages and disadvantages to each platform. This review article will examine the clinical importance of KRAS mutations in advanced colorectal cancer, and outline the various KRAS mutation detection methods.

Original languageEnglish
Pages (from-to)75-79
Number of pages5
JournalAsia-Pacific Journal of Oncology and Hematology
Volume2
Issue number1
Publication statusPublished - Feb 2010
Externally publishedYes

Keywords

  • Cetuximab
  • Colorectal carcinoma
  • KRAS mutation
  • Panitumumab
  • Polymerase chain reaction (PCR)

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