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A quantitative PCR method to detect blood microRNAs associated with tumorigenesis in transgenic mice

Alice C Fan1, Marianna M Goldrick24*, Jennifer Ho2, Yu Liang3, Pavan Bachireddy1 and Dean W Felsher1*

Author Affiliations

1 Stanford University, School of Medicine, Division of Oncology, Departments of Medicine and Pathology, CCSR building, Room 1120, 269 Campus Drive, 94305-5151 Stanford, CA, USA

2 Ambion/Applied Biosystems Inc., 2130 Woodward Suite 200, Austin, TX 78744, USA

3 Applied Biosystems Inc, Division of Molecular Cell Biology-Assay R&D, 850 Lincoln Centre Drive, Foster City, CA 94404, USA

4 BIOO Scientific, 3913 Todd Lane, Suite 312, Austin, TX 78744, USA

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Molecular Cancer 2008, 7:74  doi:10.1186/1476-4598-7-74

Published: 30 September 2008

Abstract

MicroRNA (miRNA) dysregulation frequently occurs in cancer. Analysis of whole blood miRNA in tumor models has not been widely reported, but could potentially lead to novel assays for early detection and monitoring of cancer. To determine whether miRNAs associated with malignancy could be detected in the peripheral blood, we used real-time reverse transcriptase-PCR to determine miRNA profiles in whole blood obtained from transgenic mice with c-MYC-induced lymphoma, hepatocellular carcinoma and osteosarcoma. The PCR-based assays used in our studies require only 10 nanograms of total RNA, allowing serial mini-profiles (20 – 30 miRNAs) to be carried out on individual animals over time. Blood miRNAs were measured from mice at different stages of MYC-induced lymphomagenesis and regression. Unsupervised hierarchical clustering of the data identified specific miRNA expression profiles that correlated with tumor type and stage. The miRNAs found to be altered in the blood of mice with tumors frequently reverted to normal levels upon tumor regression. Our results suggest that specific changes in blood miRNA can be detected during tumorigenesis and tumor regression.