Reliability of KRAS mutation testing in metastatic colorectal cancer patients across five laboratories

Heather Spencer Feigelson, Katrina A.B. Goddard, Monique A. Johnson, Kellyan C. Funk, Alanna Kulchak Rahm, Tia L. Kauffman, Dhananjay A. Chitale, Loic Le Marchand, C. Sue Richards

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: Mutations in the KRAS gene are associated with poor response to epidermal growth factor receptor inhibitors used in the treatment of metastatic colorectal cancer. Factors influencing KRAS test results in tumor specimens include: tumor heterogeneity, sample handling, slide preparation, techniques for tumor enrichment, DNA preparation, assay design and sensitivity. We evaluated comparability and consistency of KRAS test results among five laboratories currently being used to determine KRAS mutation status of metastatic colorectal cancer specimens in a large, multi-center observational study. Findings: Twenty formalin-fixed paraffin-embedded human colorectal cancer samples from colon resections previously tested for KRAS mutations were selected based on mutation status (6 wild type, 8 codon 12 mutations, and 6 codon 13 mutations). We found good agreement across laboratories despite differences in mutation detection methods. Eighteen of twenty samples (90%) were concordant across all five labs. Discordant results are likely not due to laboratory error, but instead to tumor heterogeneity, contamination of the tumor sample with normal tissue, or analytic factors affecting assay sensitivity. Conclusions: Our results indicate commercial and academic laboratories provide reliable results for the common KRAS gene mutations at codons 12 and 13 when an adequate percentage of tumor cells is present in the sample.

Original languageEnglish (US)
Article number196
JournalBMC Research Notes
Volume5
DOIs
StatePublished - Jun 19 2012

Keywords

  • Colorectal cancer
  • EGFR
  • KRAS
  • Laboratory error

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Reliability of KRAS mutation testing in metastatic colorectal cancer patients across five laboratories'. Together they form a unique fingerprint.

  • Cite this

    Feigelson, H. S., Goddard, K. A. B., Johnson, M. A., Funk, K. C., Rahm, A. K., Kauffman, T. L., Chitale, D. A., Le Marchand, L., & Richards, C. S. (2012). Reliability of KRAS mutation testing in metastatic colorectal cancer patients across five laboratories. BMC Research Notes, 5, [196]. https://doi.org/10.1186/1756-0500-5-196