A Multicenter Blinded Study to Evaluate KRAS Mutation Testing Methodologies in the Clinical Setting

V. Whitehall, K. Tran, A. Umapathy, F. Grieu, C. Hewitt, T.J. Evans, T. Ismail, W.Q. Li, P. Collins, P. Ravetto, B. Leggett, Manuel Salto-Tellez, R. Soong, S. Fox, R.J. Scott, A. Dobrovic, B. Iacopettat

Research output: Contribution to journalArticlepeer-review

110 Citations (Scopus)


Evidence that activating mutations of the KRAS oncogene abolish the response to anti-epidermal growth factor receptor therapy has revolutionized the treatment of advanced colorectal cancer. This has resulted in the urgent demand for KRAS mutation testing in the clinical setting to aid choice of therapy. The Am of this study was to evaluate six different KRAS mutation detection methodologies on two series of primary colorectal cancer samples. Two series of 80 frozen and 74 formalin-fixed paraffin-embedded tissue samples were sourced and DNA was extracted at a central site before distribution to seven different testing sites. KRAS mutations in codons 12 and 13 were assessed by using single strand conformation polymorphism analysis, pyrosequencing, high resolution melting analysis, dideoxy sequencing, or the commercially available TIB Molbiol (Berlin, Germany) or DxS Diagnostic innovations (Manchester, UK) kits. in frozen tissue samples, concordance in KRAS status (defined as consensus in at least five assays) was observed in 66/80 (83%) cases. In par-affin tissue, concordance was 46/74 (63%) if all assays were considered or 71/74 (96%) using the five best performing assays. These results demonstrate that a variety of detection methodologies are suitable and provide comparable results for KRAS mutation analysis of clinical samples. (J Mol Diagn 2009, 11:543-552; DOI: 10.2353/jmoldx.2009.090057)
Original languageEnglish
Pages (from-to)543-552
Number of pages10
JournalJournal of Molecular Diagnostics
Issue number6
Publication statusPublished - Nov 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Pathology and Forensic Medicine


Dive into the research topics of 'A Multicenter Blinded Study to Evaluate KRAS Mutation Testing Methodologies in the Clinical Setting'. Together they form a unique fingerprint.

Cite this