Detection and quantification of mutations in the plasma of patients with colorectal tumors.
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.
Diehl
Frank
F
Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231, USA.
Li
Meng
M
Dressman
Devin
D
He
Yiping
Y
Shen
Dong
D
Szabo
Steve
S
Diaz
Luis A
LA
Goodman
Steven N
SN
David
Kerstin A
KA
Juhl
Hartmut
H
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
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
D004273:DNA, Neoplasm