title: Detection and quantification of mutations in the plasma of patients with colorectal tumors.
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.
authors.affiliation: Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Diehl
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Devin
authors.initials: D
authors.lastname: Dressman
authors.forename: Yiping
authors.initials: Y
authors.lastname: He
authors.forename: Dong
authors.initials: D
authors.lastname: Shen
authors.forename: Steve
authors.initials: S
authors.lastname: Szabo
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.forename: Steven N
authors.initials: SN
authors.lastname: Goodman
authors.forename: Kerstin A
authors.initials: KA
authors.lastname: David
authors.forename: Hartmut
authors.initials: H
authors.lastname: Juhl
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood* / Q000378:metabolism; D005260:Female; D017491:Genes, APC; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012680:Sensitivity and Specificity
chemical_list: D004273:DNA, Neoplasm