Tumour evolution inferred by single-cell sequencing.

Nature 2011 Apr 13;472(7341):90-4. Epub 2011 Mar 13.

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.

Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse 'pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.

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http://dx.doi.org/10.1038/nature09807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504184PMC
April 2011
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References

(Supplied by CrossRef)

SY Park et al.
J. Clin. Invest. 2010

L Torres et al.
Breast Cancer Res. Treat. 2007

F Farabegoli et al.
Cytometry 2001

DY Chiang et al.
Nature Methods 2009

S Yoon et al.
Genome Res. 2009

C Alkan et al.
Nature Genet. 2009

JB Geigl et al.
Nucleic Acids Res. 2009

C Fuhrmann et al.
Nucleic Acids Res. 2008

TJ Pugh et al.
Nucleic Acids Res. 2008

BA Talseth-Palmer et al.
BMC Res. Notes 2008

S Hughes et al.
Cytogenet. Genome Res. 2004

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