Serial assessment of human tumor burdens in mice by the analysis of circulating DNA

• Published in: Cancer research (Chicago, Ill.) Vol. 67; no. 19; pp. 9364 - 9370
• Main Authors: RAGO, Carlo, HUSO, David L, DIAZ, Luis A, DIEHL, Frank, KARIM, Baktiar, GUOSHENG LIU, PAPADOPOULOS, Nickolas, SAMUELS, Yardena, VELCULESCU, Victor E, VOGELSTEIN, Bert, KINZLER, Kenneth W
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-10-2007
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Colonic Neoplasms - blood; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Disease Models, Animal; DNA Primers; DNA, Neoplasm - blood; Female; HCT116 Cells; Humans; Long Interspersed Nucleotide Elements - genetics; Medical sciences; Mice; Mice, Nude; Neoplasm Transplantation; Pharmacology. Drug treatments; Transplantation, Heterologous; Tumors; Human; Evaluation; Vertebrata; Mammalia; Mouse; Animal; DNA; Rodentia; Malignant tumor
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-07-0605

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.