title: Genomic profiling of isolated circulating tumor cells from metastatic breast cancer patients.
abstract: Molecular characterization of circulating tumor cells (CTC) 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 as well as some divergence. We showed that it is feasible to isolate CTCs away from hematopoietic cells with high purity through IE-FACS and profile them via aCGH analysis. Our approach may be used to explore genomic events involved in cancer progression and to monitor therapeutic efficacy of targeted therapies in clinical trials in a relatively noninvasive manner.
authors.affiliation: Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA 94115, USA.
authors.forename: Mark Jesus M
authors.initials: MJ
authors.lastname: Magbanua
authors.forename: Eduardo V
authors.initials: EV
authors.lastname: Sosa
authors.forename: Ritu
authors.initials: R
authors.lastname: Roy
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Eisenbud
authors.forename: Janet H
authors.initials: JH
authors.lastname: Scott
authors.forename: Adam
authors.initials: A
authors.lastname: Olshen
authors.forename: Dan
authors.initials: D
authors.lastname: Pinkel
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: John W
authors.initials: JW
authors.lastname: Park
mesh_terms: D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D002469:Cell Separation / Q000379:methods*; D055028:Comparative Genomic Hybridization; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*