期刊
BRITISH JOURNAL OF CANCER
卷 105, 期 2, 页码 246-254出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2011.197
关键词
K-Ras; mutation; dideoxy sequencing; pyrosequencing; colorectal tumour; personalised medicine
类别
资金
- Translational Medicine Research Collaboration, Cancer Research UK [C4639/A5661]
- Scottish Funding Council
- Cancer Research UK [10822] Funding Source: researchfish
BACKGROUND: The epidermal growth factor receptor-targeted monoclonal antibody cetuximab (Erbitux) was recently introduced for the treatment of metastatic colorectal cancer. Treatment response is dependent on Kirsten-Ras (K-Ras) mutation status, in which the majority of patients with tumour-specific K-Ras mutations fail to respond to treatment. Mutations in the oncogenes B-Raf and PIK3CA (phosphoinositide-3-kinase) may also influence cetuximab response, highlighting the need for a sensitive, accurate and quantitative assessment of tumour mutation burden. METHODS: Mutations in K-Ras, B-Raf and PIK3CA were identified by both dideoxy and quantitative pyrosequencing-based methods in a cohort of unselected colorectal tumours (n = 102), and pyrosequencing-based mutation calls correlated with various clinicopathological parameters. RESULTS: The use of quantitative pyrosequencing-based methods allowed us to report a 13.7% increase in mutation burden, and to identify low-frequency (<30% mutation burden) mutations not routinely detected by dideoxy sequencing. K-Ras and B-Raf mutations were mutually exclusive and independently associated with a more advanced tumour phenotype. CONCLUSION: Pyrosequencing-based methods facilitate the identification of low-frequency tumour mutations and allow more accurate assessment of tumour mutation burden. Quantitative assessment of mutation burden may permit a more detailed evaluation of the role of specific tumour mutations in the pathogenesis and progression of colorectal cancer and may improve future patient selection for targeted drug therapies. British Journal of Cancer (2011) 105, 246-254. doi: 10.1038/bjc.2011.197 www.bjcancer.com Published online 28 June 2011 (C) 2011 Cancer Research UK
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据