Detection and quantification of mutations in the plasma of patients with colorectal tumors

Frank Diehl; Meng Li; Devin Dressman; Yiping He; Dong Shen; Steve Szabo; Luis A. Diaz; Steven N. Goodman; Kerstin A. David; Hartmut Juhl; Kenneth W. Kinzler; Bert Vogelstein

doi:10.1073/pnas.0507904102

Detection and quantification of mutations in the plasma of patients with colorectal tumors

Frank Diehl, Meng Li, Devin Dressman, Yiping He, Dong Shen, Steve Szabo, Luis A. Diaz, Steven N. Goodman, Kerstin A. David, Hartmut Juhl, Kenneth W. Kinzler, Bert Vogelstein

Research output: Contribution to journal › Article › peer-review

782 Scopus citations

Abstract

The early detection of cancers through analysis of circulating DNA could have a substantial impact on morbidity and mortality. To achieve this goal, it is essential to determine the number of mutant molecules present in the circulation of cancer patients and to develop methods that are sufficiently sensitive to detect these mutations. Using a modified version of a recently developed assay for this purpose, we found that patients with advanced colorectal cancers consistently contained mutant adenomatous polyposis coli (APC) DNA molecules in their plasma. The median number of APC DNA fragments in such patients was 47,800 per ml of plasma, of which 8% were mutant. Mutant APC molecules were also detected in >60% of patients with early, presumably curable colorectal cancers, at levels ranging from 0.01% to 1.7% of the total APC molecules. These results have implications for the mechanisms through which tumor DNA is released into the circulation and for diagnostic tests based on this phenomenon.

Original language	English (US)
Pages (from-to)	16368-16373
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	45
DOIs	https://doi.org/10.1073/pnas.0507904102
State	Published - Nov 8 2005

Keywords

Circulating DNA
Colorectal cancer
Diagnosis
Plasma DNA
Tumor suppressor gene

ASJC Scopus subject areas

General

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10.1073/pnas.0507904102

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Diehl, F., Li, M., Dressman, D., He, Y., Shen, D., Szabo, S., Diaz, L. A., Goodman, S. N., David, K. A., Juhl, H., Kinzler, K. W., & Vogelstein, B. (2005). Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proceedings of the National Academy of Sciences of the United States of America, 102(45), 16368-16373. https://doi.org/10.1073/pnas.0507904102

Diehl, F, Li, M, Dressman, D, He, Y, Shen, D, Szabo, S, Diaz, LA, Goodman, SN, David, KA, Juhl, H, Kinzler, KW & Vogelstein, B 2005, 'Detection and quantification of mutations in the plasma of patients with colorectal tumors', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 45, pp. 16368-16373. https://doi.org/10.1073/pnas.0507904102

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abstract = "The early detection of cancers through analysis of circulating DNA could have a substantial impact on morbidity and mortality. To achieve this goal, it is essential to determine the number of mutant molecules present in the circulation of cancer patients and to develop methods that are sufficiently sensitive to detect these mutations. Using a modified version of a recently developed assay for this purpose, we found that patients with advanced colorectal cancers consistently contained mutant adenomatous polyposis coli (APC) DNA molecules in their plasma. The median number of APC DNA fragments in such patients was 47,800 per ml of plasma, of which 8% were mutant. Mutant APC molecules were also detected in >60% of patients with early, presumably curable colorectal cancers, at levels ranging from 0.01% to 1.7% of the total APC molecules. These results have implications for the mechanisms through which tumor DNA is released into the circulation and for diagnostic tests based on this phenomenon.",

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AU - Diaz, Luis A.

AU - Goodman, Steven N.

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AU - Vogelstein, Bert

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AB - The early detection of cancers through analysis of circulating DNA could have a substantial impact on morbidity and mortality. To achieve this goal, it is essential to determine the number of mutant molecules present in the circulation of cancer patients and to develop methods that are sufficiently sensitive to detect these mutations. Using a modified version of a recently developed assay for this purpose, we found that patients with advanced colorectal cancers consistently contained mutant adenomatous polyposis coli (APC) DNA molecules in their plasma. The median number of APC DNA fragments in such patients was 47,800 per ml of plasma, of which 8% were mutant. Mutant APC molecules were also detected in >60% of patients with early, presumably curable colorectal cancers, at levels ranging from 0.01% to 1.7% of the total APC molecules. These results have implications for the mechanisms through which tumor DNA is released into the circulation and for diagnostic tests based on this phenomenon.

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Detection and quantification of mutations in the plasma of patients with colorectal tumors

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