title: Circulating mutant DNA to assess tumor dynamics.
abstract: 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.
authors.affiliation: 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.
authors.forename: Frank
authors.initials: F
authors.lastname: Diehl
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schmidt
authors.forename: Michael A
authors.initials: MA
authors.lastname: Choti
authors.forename: Katharine
authors.initials: K
authors.lastname: Romans
authors.forename: Steven
authors.initials: S
authors.lastname: Goodman
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Katherine
authors.initials: K
authors.lastname: Thornton
authors.forename: Nishant
authors.initials: N
authors.lastname: Agrawal
authors.forename: Lori
authors.initials: L
authors.lastname: Sokoll
authors.forename: Steve A
authors.initials: SA
authors.lastname: Szabo
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
mesh_terms: 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
chemical_list: D015415:Biomarkers; D004273:DNA, Neoplasm; D005456:Fluorescent Dyes