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Comparative Genomic Hybridization, Loss of Heterozygosity, and DNA Sequence Analysis of Single Cells

Christoph A. Klein, Oleg Schmidt-Kittler, Julian A. Schardt, Klaus Pantel, Michael R. Speicher and Gert Riethmüller
Proceedings of the National Academy of Sciences of the United States of America
Vol. 96, No. 8 (Apr. 13, 1999), pp. 4494-4499
Stable URL: http://www.jstor.org/stable/47594
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Comparative Genomic Hybridization, Loss of Heterozygosity, and DNA Sequence Analysis of Single Cells
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Abstract

A PCR strategy is described for global amplification of DNA from a single eukaryotic cell that enables the comprehensive analysis of the whole genome. By comparative genomic hybridization, not only gross DNA copy number variations, such as monosomic X and trisomic 21 in single male cells and cells from Down's syndrome patients, respectively, but multiple deletions and amplifications characteristic for human tumor cells are reliably retrieved. As a model of heterogeneous cell populations exposed to selective pressure, we have studied single micrometastatic cells isolated from bone marrow of cancer patients. The observed congruent pattern of comparative genomic hybridization data, loss of heterozygosity, and mutations as detected by sequencing attests to the technique's fidelity and demonstrates its usefulness for assessing clonal evolution of genetic variants in complex populations.

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