Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients.

作者: T.-L. Wang , L. A. Diaz , K. Romans , A. Bardelli , S. Saha

DOI: 10.1073/PNAS.0308716101

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摘要: Resistance to chemotherapy is a major cause of mortality in advanced cancer patients. In this study, digital karyotyping was used search for genomic alterations liver metastases that were clinically resistant 5-fluorouracil (5-FU). two four patients, we identified amplification an ≈100-kb region on 18p11.32 particular interest because it contained the gene encoding thymidylate synthase (TYMS), molecular target 5-FU. Analysis TYMS by fluorescence situ hybridization 23% 31 5-FU-treated cancers, whereas no observed patients had not been treated with Patients containing substantially shorter median survival (329 days) than those without (1,021 days, P <0.01). These data suggest genetic mechanism 5-FU resistance vivo and have important implications management colorectal recurrent disease.

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