Inferring tumor progression from genomic heterogeneity

Navin, N. E., Krasnitz, A., Rodgers, L., Cook, K., Meth, J. L., Kendall, J. T., Riggs, M., Eberling, Y., Troge, J. E., Grubor, V., Levy, D., Lundin, P., Månér, S., Zetterberg, A., Hicks, J. B., Wigler, M. H. (January 2010) Inferring tumor progression from genomic heterogeneity. Genome Research, 20 (1). pp. 68-80.

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DOI: 10.1101/gr.099622.109


Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth. © 2010 by Cold Spring Harbor Laboratory Press.

Item Type: Paper
Uncontrolled Keywords: tumor progression Sector-Ploidy-Profiling (SPP) comparative genomic HYBRIDIZATION (CGH)
Subjects: bioinformatics > genomics and proteomics
diseases & disorders > cancer > cancer types > breast cancer
organism description > animal > mammal > primates > hominids > human
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Instrumentation Service
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL labs > Hicks lab
CSHL labs > Krasnitz lab
CSHL labs > Levy lab
CSHL labs > Wigler lab
School of Biological Sciences > Publications
Depositing User: CSHL Librarian
Date: January 2010
Date Deposited: 05 Oct 2011 15:18
Last Modified: 07 Jan 2019 16:54
PMCID: PMC2798832
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