Circulating mutant DNA to assess tumor dynamics.
The measurement of circulating nucleic acids has transformed the management of chronic viral infections such as HIV. The development of analogous markers for individuals with cancer could similarly enhance the management of their disease. DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. In this study, we applied a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in 162 plasma samples from 18 subjects undergoing multimodality therapy for colorectal cancer. We found that ctDNA measurements could be used to reliably monitor tumor dynamics in subjects with cancer who were undergoing surgery or chemotherapy. We suggest that this personalized genetic approach could be generally applied to individuals with other types of cancer.
Diehl
Frank
F
The Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center at the Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
Schmidt
Kerstin
K
Choti
Michael A
MA
Romans
Katharine
K
Goodman
Steven
S
Li
Meng
M
Thornton
Katherine
K
Agrawal
Nishant
N
Sokoll
Lori
L
Szabo
Steve A
SA
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Diaz
Luis A
LA
D015415:Biomarkers / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000097:blood*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D008280:Magnetics; D025202:Molecular Diagnostic Techniques; D021141:Nucleic Acid Amplification Techniques; D012008:Recurrence
D015415:Biomarkers; D004273:DNA, Neoplasm; D005456:Fluorescent Dyes