Circulating mutant DNA to assess tumor dynamics

被引：2326

作者：

Diehl, Frank ^{[1
,2
]}

Schmidt, Kerstin ^{[1
,2
]}

Choti, Michael A. ^{[3
]}

Romans, Katharine ^{[1
,2
]}

Goodman, Steven ^{[4
]}

Li, Meng ^{[1
,2
]}

Thornton, Katherine ^{[1
,2
]}

Agrawal, Nishant ^{[1
,2
]}

Sokoll, Lori ^{[5
]}

Szabo, Steve A. ^{[1
,2
]}

Kinzler, Kenneth W. ^{[1
,2
]}

Vogelstein, Bert ^{[1
,2
]}

Diaz, Luis A., Jr. ^{[1
,2
]}

机构：

[1] Johns Hopkins Med Inst, Howard Hughes Med Inst, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA

[2] Johns Hopkins Med Inst, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA

[3] Johns Hopkins Med Inst, Dept Surg, Baltimore, MD 21205 USA

[4] Johns Hopkins Med Inst, Dept Biostat, Baltimore, MD 21205 USA

[5] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA

来源：

NATURE MEDICINE | 2008年 / 14卷 / 09期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/nm.1789

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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.

引用

页码：985 / 990

页数：6

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