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

被引：32
作者：
Deschoolmeester, V. [1 ]
Boeckx, C. [1 ]
Baay, M. [1 ]
Weyler, J. [2 ]
Wuyts, W. [3 ]
Van Marck, E. [4 ]
Peeters, M. [1 ]
Lardon, F. [1 ]
Vermorken, J. B. [1 ]
机构：
[1] Univ Antwerp, Univ Antwerp Hosp, Dept Med Oncol, Lab Canc Res & Clin Oncol, B-2610 Antwerp, Belgium
[2] Univ Antwerp, Dept Epidemiol & Social Med, B-2610 Antwerp, Belgium
[3] Univ Antwerp, Univ Antwerp Hosp, Dept Med Genet, B-2610 Antwerp, Belgium
[4] Univ Antwerp Hosp, Dept Pathol, B-2650 Edegem, Belgium
来源：
BRITISH JOURNAL OF CANCER | 2010年 / 103卷 / 10期
关键词：
colorectal cancer; high-resolution melting analysis; prognosis; KRAS; survival analysis; KIRSTEN RAS MUTATIONS; K-RAS; MICROSATELLITE INSTABILITY; COLON-CANCER; GENE-MUTATIONS; BRAF; STAGE; CHEMOTHERAPY; CARCINOMAS; METASTASES;
D O I：
10.1038/sj.bjc.6605959
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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. British Journal of Cancer (2010) 103, 1627-1636. doi:10.1038/sj.bjc.6605959 www.bjcancer.com Published online 19 October 2010 (C) 2010 Cancer Research UK
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收藏
页码：1627 / 1636
页数：10
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