Circulating mutant DNA to assess tumor dynamics

Frank Diehl, Kerstin Schmidt, Michael A. Choti, Katharine Romans, Steven Goodman, Meng Li, Katherine Thornton, Nishant Agrawal, Lori Sokoll, Steve A. Szabo, Kenneth W. Kinzler, Bert Vogelstein, Luis A. Diaz

Research output: Contribution to journalArticle

1219 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)985-990
Number of pages6
JournalNature medicine
Volume14
Issue number9
DOIs
StatePublished - Sep 1 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Diehl, F., Schmidt, K., Choti, M. A., Romans, K., Goodman, S., Li, M., Thornton, K., Agrawal, N., Sokoll, L., Szabo, S. A., Kinzler, K. W., Vogelstein, B., & Diaz, L. A. (2008). Circulating mutant DNA to assess tumor dynamics. Nature medicine, 14(9), 985-990. https://doi.org/10.1038/nm.1789