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Title
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**KRAS** mutation detection and prognostic potential in sporadic colorectal cancer using high-resolution melting analysis
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Author
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Abstract
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| Background: The development of targeted therapies has created a pressing clinical need for molecular characterisation of cancers. In this retrospective study, high-resolution melting analysis (HRMA) was validated and implemented for screening of 164 colorectal cancer (CRC) patients to detect KRAS hot-spot mutations and to evaluate its prognostic value. Direct sequencing was used to confirm and characterise HRMA results. Methods: After establishing its sensitivity, HRMA was validated on seven cell lines and inter- and intra-variation were analysed. The prognostic value of KRAS mutations in CRC was evaluated using survival analysis. Results: HRMA revealed abnormal melting patterns in 34.1% CRC samples. KaplanMeier survival curves revealed a significantly shorter overall (OS) and disease-free survival (DFS) for CRC patients harbouring a KRAS mutation. In the Cox regression analysis, only when colon and rectal cancer were analysed separately, KRAS mutation was a negative predictor for OS in patients with rectal cancer and DFS in those with stage II colon cancer. Conclusions: HRMA was found to be a valid screening method for KRAS mutation detection. The KRAS mutation came forward as a negative predictive factor for OS in patients with rectal cancer and for DFS in stage II colon cancer patients. |
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Language
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English
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Source (journal)
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The British journal of cancer. - London
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Publication
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London
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2010
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ISSN
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0007-0920
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DOI
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10.1038/SJ.BJC.6605959
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Volume/pages
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103
:9
(2010)
, p. 1627-1636
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ISI
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000286119700022
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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