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Br J Cancer. 2010 Nov 9;103(10):1627-36. doi: 10.1038/sj.bjc.6605959. Epub 2010 Oct 19.

KRAS mutation detection and prognostic potential in sporadic colorectal cancer using high-resolution melting analysis.

Author information

1
Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp/Antwerp University Hospital, Wilrijk 2610, Belgium. vanessa.deschoolmeester@ua.ac.be

Abstract

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. Kaplan-Meier 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.

PMID:
20959826
PMCID:
PMC2990591
DOI:
10.1038/sj.bjc.6605959
[Indexed for MEDLINE]
Free PMC Article

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