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Technical Report
Nature Medicine 14, 985 - 990 (2008)
Published online: 31 July 2007 | doi:10.1038/nm.1789
Circulating mutant DNA to assess tumor dynamics
Frank Diehl1,5, Kerstin Schmidt1,5, Michael A Choti2, Katharine Romans1, Steven Goodman3, Meng Li1, Katherine Thornton1, Nishant Agrawal1, Lori Sokoll4, Steve A Szabo1, Kenneth W Kinzler1, Bert Vogelstein1 & Luis A Diaz Jr1
Abstract
The measurement of circulating nucleic acids has transformed the management of chronic viral infections such as HIV. The development of analogous markers for individuals with cancer could similarly enhance the management of their disease. DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. In this study, we applied a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in 162 plasma samples from 18 subjects undergoing multimodality therapy for colorectal cancer. We found that ctDNA measurements could be used to reliably monitor tumor dynamics in subjects with cancer who were undergoing surgery or chemotherapy. We suggest that this personalized genetic approach could be generally applied to individuals with other types of cancer (pages 914–915).
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