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

doi:10.1038/nm.1789

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

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2089 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 language	English (US)
Pages (from-to)	985-990
Number of pages	6
Journal	Nature medicine
Volume	14
Issue number	9
DOIs	https://doi.org/10.1038/nm.1789
State	Published - Sep 2008

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1038/nm.1789

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title = "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 (pages 914-915).",

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

note = "Funding Information: We thank G.Traverso for useful discussions; D. Heslop, C. Vaughn and D. Edelstein for their help with plasma collection; and L. Fayad for help with the interpretation of imaging studies. This work was supported by the Virginia and D.K. Ludwig Fund for Cancer Research, the Miracle Foundation, the US National Colorectal Cancer Research Alliance and US National Institutes of Health grants CA43460, CA57345, CA62924 and CA129825.",

year = "2008",

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doi = "10.1038/nm.1789",

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AU - Thornton, Katherine

AU - Agrawal, Nishant

AU - Sokoll, Lori

AU - Szabo, Steve A.

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Diaz, Luis A.

N1 - Funding Information: We thank G.Traverso for useful discussions; D. Heslop, C. Vaughn and D. Edelstein for their help with plasma collection; and L. Fayad for help with the interpretation of imaging studies. This work was supported by the Virginia and D.K. Ludwig Fund for Cancer Research, the Miracle Foundation, the US National Colorectal Cancer Research Alliance and US National Institutes of Health grants CA43460, CA57345, CA62924 and CA129825.

PY - 2008/9

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Circulating mutant DNA to assess tumor dynamics

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