Inferring tumor progression from genomic heterogeneity
Clicks: 150
ID: 273923
2009
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.
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wigler2009genomeinferring
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| Authors | Nicholas Navin,Alexander Krasnitz,Linda Rodgers,Kerry Cook,Jennifer Meth,Jude Kendall,Michael Riggs,Yvonne Eberling,Jennifer Troge,Vladimir Grubor,Dan Levy,Pär Lundin,Susanne Månér,Anders Zetterberg,James Hicks,Michael Wigler;Nicholas Navin;Alexander Krasnitz;Linda Rodgers;Kerry Cook;Jennifer Meth;Jude Kendall;Michael Riggs;Yvonne Eberling;Jennifer Troge;Vladimir Grubor;Dan Levy;Pär Lundin;Susanne Månér;Anders Zetterberg;James Hicks;Michael Wigler; |
| Journal | genome research |
| Year | 2009 |
| DOI | 10.1101/gr.099622.109 |
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