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Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16368-73. Epub 2005 Oct 28.

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

Author information

1
Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231, USA.

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.

PMID:
16258065
PMCID:
PMC1283450
DOI:
10.1073/pnas.0507904102
[Indexed for MEDLINE]
Free PMC Article

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