Polzer, Bernhard and Medoro, Gianni and Pasch, Sophie and Fontana, Francesca and Zorzino, Laura and Pestka, Aurelia and Andergassen, Ulrich and Meier-Stiegen, Franziska and Czyz, Zbigniew T. and Alberter, Barbara and Treitschke, Steffi and Schamberger, Thomas and Sergio, Maximilian and Bregola, Giulia and Doffini, Anna and Gianni, Stefano and Calanca, Alex and Signorini, Giulio and Bolognesi, Chiara and Hartmann, Arndt and Fasching, Peter A. and Sandri, Maria T. and Rack, Brigitte and Fehm, Tanja and Giorgini, Giuseppe and Manaresi, Nicolo and Klein, Christoph A. (2014) Molecular profiling of single circulating tumor cells with diagnostic intention. EMBO MOLECULAR MEDICINE, 6 (11). pp. 1371-1386. ISSN 1757-4676, 1757-4684
Full text not available from this repository. (Request a copy)Abstract
Several hundred clinical trials currently explore the role of circulating tumor cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterization of CTCs with diagnostic precision. We therefore combined a workflow for enrichment and isolation of pure CTCs with a non-random whole genome amplification method for single cells and applied it to 510 single CTCs and 189 leukocytes of 66 CTC-positive breast cancer patients. We defined a genome integrity index (GII) to identify single cells suited for molecular characterization by different molecular assays, such as diagnostic profiling of point mutations, gene amplifications and whole genomes of single cells. The reliability of >90% for successful molecular analysis of high-quality clinical samples selected by the GII enabled assessing the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumors and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre-existing cells resistant to ERBB2-targeted therapies suggesting ongoing microevolution at late-stage disease whose exploration may provide essential information for personalized treatment decisions and shed light into mechanisms of acquired drug resistance.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | METASTATIC BREAST-CANCER; RESISTANT PROSTATE-CANCER; PERIPHERAL-BLOOD; PIK3CA MUTATIONS; GENOMIC ANALYSIS; GENETIC-ANALYSIS; PROGRESSION; TRASTUZUMAB; DIVERSITY; EVOLUTION; breast cancer; circulating tumor cells; metastasis; single cell analysis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Aug 2019 15:00 |
| Last Modified: | 08 Aug 2019 15:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9282 |
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