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Combined transcriptome and genome analysis of single micrometastatic cells

Abstract

In human cancer, early systemic spread of tumor cells is recognized as a leading cause of death. Adjuvant therapies are administered to patients after complete resectioning of their primary tumors to eradicate the few residual and latent metastatic cells. These therapeutic regimens, however, are currently designed without direct information about the presence or nature of the latent cells. To address this problem, we developed a PCR-based technique to analyze the transcriptome of individual tumor cells isolated from the bone marrow of cancer patients. From the same cells, genomic aberrations were identified by comparative genomic hybridization. The utility of this approach for understanding the biology of occult disseminated cells and for the identification of new therapeutic targets is demonstrated here by the detection of frequent extracellular matrix metalloproteinase inducer (EMMPRIN; CD147) expression which was verified by immunostaining.

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Figure 1: Titration of minimal mRNA for global amplification and array analysis.
Figure 2: Expression of EEF1A1, NFKB, IKBA, MMP14, and TNFA in single MM6 cells.
Figure 3: EMMPRIN detection.

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Acknowledgements

We thank V. Horejsi for the MEM 6/2 antibody, B. Lehnert, S. Pentz, and M. Wüllner for excellent technical assistance, and J. Johnson, K. Fellenberg, C. Itin, C. Ahrens, and D. Zohlnhöfer for their help. This work was supported by the SFB 469, SFB 456, the Wilhelm-Sander Stiftung, and a grant co-funded by Micromet AG, Germany, and the German Federal Ministry for Education, Science, Research and Technology.

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Correspondence to Christoph A. Klein.

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Klein, C., Seidl, S., Petat-Dutter, K. et al. Combined transcriptome and genome analysis of single micrometastatic cells. Nat Biotechnol 20, 387–392 (2002). https://doi.org/10.1038/nbt0402-387

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  • DOI: https://doi.org/10.1038/nbt0402-387

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