title: Serial assessment of human tumor burdens in mice by the analysis of circulating DNA.
abstract: Internal human xenografts provide valuable animal models to study the microenvironments and metastatic processes occurring in human cancers. However, the use of such models is hampered by the logistical difficulties of reproducibly and simply assessing tumor burden. We developed a high-sensitivity assay for quantifying human DNA in small volumes of mouse plasma, enabling in-life monitoring of systemic tumor burden. Growth kinetics analyses of various xenograft models showed the utility of circulating human DNA as a biomarker. We found that human DNA concentration reproducibly increased with disease progression and decreased after successful therapeutic intervention. A marked, transient spike in circulating human tumor DNA occurred immediately after cytotoxic therapy or surgery. This simple assay may find broad utility in target validation studies and preclinical drug development programs.
authors.affiliation: The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute, Baltimore, Maryland, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Rago
authors.forename: David L
authors.initials: DL
authors.lastname: Huso
authors.forename: Frank
authors.initials: F
authors.lastname: Diehl
authors.forename: Baktiar
authors.initials: B
authors.lastname: Karim
authors.forename: Guosheng
authors.initials: G
authors.lastname: Liu
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: Yardena
authors.initials: Y
authors.lastname: Samuels
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D003110:Colonic Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm