Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Dijkstra, JR; Heideman, DA; Meijer, GA; Boers, JE; 't Hart, NA; Diebold, J; Hirschmann, A; Hoefler, G; Winter, G; Miltenberger-Miltenyi, G; Pereira, SV; Richman, SD; Quirke, P; Rouleau, EL; Guinebretiere, JM; Tejpar, S; Biesmans, B; van Krieken, JH.
KRAS mutation analysis on low percentage of colon cancer cells: the importance of quality assurance.
Virchows Arch. 2013; 462(1):39-46
Doi: 10.1007/s00428-012-1356-2
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PubMed
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- Co-authors Med Uni Graz
- Höfler Gerald
- Winter Gerlinde
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- Abstract:
- KRAS mutation testing is mandatory for patients with metastatic colorectal cancer who are eligible for treatment with an epidermal growth factor receptor targeting agent, since tumors with a mutation are not sensitive to the drug. Several methods for mutation testing are in use and the need for external quality assurance has been demonstrated. An often little addressed but important issue in external quality assurance schemes is a low percentage of tumor cells in the test samples, where the analytical sensitivity of most tests becomes critical. Using artificial samples based on a mixture of cell lines with known mutation status of the KRAS gene, we assessed the reliability of a series of commonly used methods (Sanger sequencing, high resolution melting, pyrosequencing, and amplification refractory mutation system-polymerase chain reaction) on samples with 0, 2.5, 5, 10, and 15 % mutated cells. Nine laboratories throughout Europe participated and submitted a total of ten data sets. The limit of detection of each method differed, ranging from >15-5 % tumor cells. All methods showed a decreasing correct mutation call rate proportionally with decreasing percentage of tumor cells. Our findings indicate that laboratories and clinicians need to be aware of the decrease in correct mutation call rate proportionally with decreasing percentage of tumor cells and that external quality assurance schemes need to address the issue of low tumor cell percentage in the test samples.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenocarcinoma - genetics Adenocarcinoma - pathology
- Cell Count -
- Cell Line, Tumor -
- Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology
- DNA Mutational Analysis - methods DNA Mutational Analysis - standards
- DNA, Neoplasm - analysis
- Genes, ras -
- Humans -
- Limit of Detection -
- Molecular Diagnostic Techniques - methods Molecular Diagnostic Techniques - standards
- Mutation -
- Polymerase Chain Reaction - methods Polymerase Chain Reaction - standards
- Proto-Oncogene Proteins - genetics
- Quality Assurance, Health Care - methods Quality Assurance, Health Care - standards
- Reproducibility of Results -
- ras Proteins - genetics
- Find related publications in this database (Keywords)
- KRAS
- Mutation
- Colon cancer
- EQA