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. 2012:5:15-22.
doi: 10.4137/CPath.S8798. Epub 2012 May 15.

Comparison of KRAS Mutation Assessment in Tumor DNA and Circulating Free DNA in Plasma and Serum Samples

Shethah R Morgan  1 , Jessica Whiteley, Emma Donald, John Smith, Marcia T Eisenberg, Eddie Kallam, Lauren Kam-Morgan
Affiliations

Comparison of KRAS Mutation Assessment in Tumor DNA and Circulating Free DNA in Plasma and Serum Samples

Shethah R Morgan et al. Clin Med Insights Pathol. 2012.

Abstract

Testing for mutations in the KRAS oncogene for patients with metastatic colorectal cancer (mCRC) is generally performed using DNA from formalin-fixed paraffin-embedded tumor tissue; however, access to specimens can be limited and analysis challenging. This study assessed the identification of KRAS mutations in circulating free DNA (cfDNA) using a commercially available KRAS polymerase chain reaction (PCR) kit. Matched plasma, serum and tumor samples were available from 71 patients with mCRC who had received prior therapy but whose disease progressed following therapy. Yields of cfDNA from plasma and serum samples were comparable. Analyses were successful in 70/71 plasma-extracted samples (specificity: 97%, sensitivity: 31%) and 67/71 serum- extracted samples (specificity: 100%, sensitivity: 25%). This study demonstrates that KRAS mutations can be detected in cfDNA using a commercially available KRAS PCR kit, confirming cfDNA as a potential alternative source of tumor DNA in a diagnostic setting if access to archival tumor specimens is limited.

Keywords: KRAS; cfDNA; colorectal cancer; mutation.

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Figures

Figure 1
Figure 1
Frequency of specific KRAS mutations in FFPE tumor samples. The PCR kit used in the analysis could detect seven mutations in codons 12 and 13 of KRAS. Note: Samples from 109 patients were analyzed; data are shown for the 48 M+ samples.
Figure 2
Figure 2
Mutation threshold cycle (Ct) values in plasma- and serum-extracted cfDNA samples.
Figure 3
Figure 3
Comparison of parameters determining KRAS mutation detection utility between cfDNA plasma and serum samples (M+ Confidence Level 3). Abbreviations: NPV, negative predictive value; PPV, positive predictive value; T, tumour.
See this image and copyright information in PMC

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