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 journalArticle

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 languageEnglish (US)
Pages (from-to)16368-16373
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number45
DOIs
StatePublished - Nov 8 2005

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Adenomatous Polyposis Coli
Colorectal Neoplasms
Mutation
DNA
Early Detection of Cancer
Routine Diagnostic Tests
Neoplasms
Morbidity
Mortality

Keywords

  • Circulating DNA
  • Colorectal cancer
  • Diagnosis
  • Plasma DNA
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Detection and quantification of mutations in the plasma of patients with colorectal tumors. / Diehl, Frank; Li, Meng; Dressman, Devin; He, Yiping; Shen, Dong; Szabo, Steve; Diaz, Luis A.; Goodman, Steven N.; David, Kerstin A.; Juhl, Hartmut; Kinzler, Kenneth W; Vogelstein, Bert.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 45, 08.11.2005, p. 16368-16373.

Research output: Contribution to journalArticle

Diehl, Frank ; Li, Meng ; Dressman, Devin ; He, Yiping ; Shen, Dong ; Szabo, Steve ; Diaz, Luis A. ; Goodman, Steven N. ; David, Kerstin A. ; Juhl, Hartmut ; Kinzler, Kenneth W ; Vogelstein, Bert. / Detection and quantification of mutations in the plasma of patients with colorectal tumors. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 45. pp. 16368-16373.
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