Circulating mutant DNA to assess tumor dynamics.

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.

• Authors: 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 Jr
• Journal: Nature medicine (Nat Med) Vol. 14 Issue 9 Pg. 985-90 (Sep 2008) ISSN: 1546-170X [Electronic] United States
• PMID: 18670422 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Biomarkers
• DNA, Neoplasm
• Fluorescent Dyes

Topics

• Biomarkers (blood)
• Colorectal Neoplasms (blood, drug therapy, genetics, therapy)
• DNA Mutational Analysis (methods)
• DNA, Neoplasm (blood)
• Flow Cytometry
• Fluorescent Dyes
• Humans
• Magnetics
• Molecular Diagnostic Techniques
• Nucleic Acid Amplification Techniques
• Recurrence