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Published online first on November 7, 2012
[Cancer Research, 10.1158/0008-5472.CAN-11-3017]
© 2012 American Association for Cancer Research
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Research Article

Genomic profiling of isolated circulating tumor cells from metastatic breast cancer patients

Mark Jesus M. Magbanua1, Eduardo V. Sosa1, Ritu Roy2, Lauren E. Eisenbud1, Janet H. Scott1, Adam Olshen3, Dan Pinkel4, Hope Rugo5, and John W. Park6,*

1 Hematology/Oncology, University of California San Francisco
2 Medicine, UCSF
3 Epidemiology and Biostatistics, University of California San Francisco
4 Dept of Laboratory Medicine, University of California
5 Medicine, University of California San Francisco
6 Hematology Oncology, UCSF Cancer Center

* Corresponding Author: John W. Park, Hematology Oncology, UCSF Cancer Center, 2nd Floor, 1600 Divisadero Street, San Francisco, CA, 94115-1710, United States jpark{at}cc.ucsf.edu

Molecular characterization of circulating tumor cells (CTCs) from blood is technically challenging because cells are rare and difficult to isolate. We developed a novel approach to isolate CTCs from blood via immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS). Isolated CTCs were subjected to genome-wide copy number analysis via array comparative genomic hybridization (aCGH). In clinical studies, CTCs were isolated from 181 patients with metastatic breast cancer, 102 of which were successfully profiled, including matched archival primary tumor from five patients. CTCs revealed a wide range of copy number alterations including those previously reported in breast cancer. Comparison with two published aCGH datasets of primary breast tumors revealed similar frequencies of recurrent genomic copy number aberrations. In addition, serial testing of CTCs confirmed reproducibility and indicated genomic change over time. Comparison of CTCs with matched archival primary tumors confirmed shared lineage with notable divergence. We demonstrate that it is feasible to isolate CTCs away from hematopoietic cells with high purity via IE/FACS and profile them via aCGH analysis. Our approach may be utilized to explore genomic events involved in cancer progression and to monitor therapeutic efficacy of targeted therapies in clinical trials in a relatively non-invasive manner.




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