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Br J Cancer ; 103(10): 1627-36, 2010 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-20959826

RESUMO

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.


Assuntos
Neoplasias Colorretais/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Primers do DNA , DNA de Neoplasias/genética , Variação Genética , Humanos , Programas de Rastreamento/métodos , Mutação , Desnaturação de Ácido Nucleico , Reação em Cadeia da Polimerase , Prognóstico , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias Retais/genética , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Análise de Regressão , Análise de Sobrevida
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