Molecular profiling of single circulating tumor cells with diagnostic intention.

Autor: Polzer B; Project Group 'Personalized Tumor Therapy', Fraunhofer Institute for Toxicology und Experimental Medicine, Regensburg, Germany., Medoro G; Silicon Biosystems S.p.A., Bologna, Italy., Pasch S; Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany., Fontana F; Silicon Biosystems S.p.A., Bologna, Italy., Zorzino L; Division of Laboratory Medicine, European Institute of Oncology, Milan, Italy., Pestka A; Department of Gynecology and Obstetrics, University Munich, Munich, Germany., Andergassen U; Department of Gynecology and Obstetrics, University Munich, Munich, Germany., Meier-Stiegen F; Department of Gynecology and Obstetrics, University of Düsseldorf, Düsseldorf, Germany., Czyz ZT; Project Group 'Personalized Tumor Therapy', Fraunhofer Institute for Toxicology und Experimental Medicine, Regensburg, Germany Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany., Alberter B; Project Group 'Personalized Tumor Therapy', Fraunhofer Institute for Toxicology und Experimental Medicine, Regensburg, Germany., Treitschke S; Project Group 'Personalized Tumor Therapy', Fraunhofer Institute for Toxicology und Experimental Medicine, Regensburg, Germany., Schamberger T; Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany., Sergio M; Silicon Biosystems S.p.A., Bologna, Italy., Bregola G; Silicon Biosystems S.p.A., Bologna, Italy., Doffini A; Silicon Biosystems S.p.A., Bologna, Italy., Gianni S; Silicon Biosystems S.p.A., Bologna, Italy., Calanca A; Silicon Biosystems S.p.A., Bologna, Italy., Signorini G; Silicon Biosystems S.p.A., Bologna, Italy., Bolognesi C; Silicon Biosystems S.p.A., Bologna, Italy., Hartmann A; Department of Pathology, University Erlangen, Erlangen, Germany., Fasching PA; Department of Gynecology and Obstetrics, University Erlangen, Erlangen, Germany., Sandri MT; Division of Laboratory Medicine, European Institute of Oncology, Milan, Italy., Rack B; Department of Gynecology and Obstetrics, University Munich, Munich, Germany., Fehm T; Department of Gynecology and Obstetrics, University of Düsseldorf, Düsseldorf, Germany., Giorgini G; Silicon Biosystems S.p.A., Bologna, Italy., Manaresi N; Silicon Biosystems S.p.A., Bologna, Italy., Klein CA; Project Group 'Personalized Tumor Therapy', Fraunhofer Institute for Toxicology und Experimental Medicine, Regensburg, Germany Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany christoph.klein@klinik.uni-regensburg.de.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2014 Nov; Vol. 6 (11), pp. 1371-86.
DOI: 10.15252/emmm.201404033
Abstrakt: 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.
(© 2014 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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