Reliability of <it>KRAS</it> mutation testing in metastatic colorectal cancer patients across five laboratories

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>KRAS</it> gene are associated with poor response to epidermal growth factor receptor inhibitors used in the treatment of metastatic colorectal cancer. Factors influencing <it>KRAS</it> tes...

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Bibliographic Details
Main Authors: Feigelson Heather, Goddard Katrina AB, Johnson Monique A, Funk Kellyan C, Rahm Alanna, Kauffman Tia L, Chitale Dhananjay A, Le Marchand Loic, Richards C
Format: Article
Language:English
Published: BMC 2012-04-01
Series:BMC Research Notes
Subjects:
Online Access:http://www.biomedcentral.com/1756-0500/5/196
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Summary:<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>KRAS</it> gene are associated with poor response to epidermal growth factor receptor inhibitors used in the treatment of metastatic colorectal cancer. Factors influencing <it>KRAS</it> 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 <it>KRAS</it> test results among five laboratories currently being used to determine <it>KRAS</it> mutation status of metastatic colorectal cancer specimens in a large, multi-center observational study.</p> <p>Findings</p> <p>Twenty formalin-fixed paraffin-embedded human colorectal cancer samples from colon resections previously tested for <it>KRAS</it> 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.</p> <p>Conclusions</p> <p>Our results indicate commercial and academic laboratories provide reliable results for the common <it>KRAS</it> gene mutations at codons 12 and 13 when an adequate percentage of tumor cells is present in the sample.</p>
ISSN:1756-0500