Genetic clonal diversity predicts progression to esophageal adenocarcinoma (original) (raw)

Nature Genetics volume 38, pages 468–473 (2006)Cite this article

Abstract

Neoplasms are thought to progress to cancer through genetic instability generating cellular diversity1,2 and clonal expansions driven by selection for mutations in cancer genes3,4. Despite advances in the study of molecular biology of cancer genes5, relatively little is known about evolutionary mechanisms that drive neoplastic progression. It is unknown, for example, which may be more predictive of future progression of a neoplasm: genetic homogenization of the neoplasm, possibly caused by a clonal expansion, or the accumulation of clonal diversity. Here, in a prospective study, we show that clonal diversity measures adapted from ecology and evolution can predict progression to adenocarcinoma in the premalignant condition known as Barrett's esophagus, even when controlling for established genetic risk factors, including lesions in TP53 (p53; ref. 6) and ploidy abnormalities7. Progression to cancer through accumulation of clonal diversity, on which natural selection acts, may be a fundamental principle of neoplasia with important clinical implications.

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Acknowledgements

We thank R. Klausner, S. Self, S. Moolgavkar and H. Tang for their helpful suggestions. This work was supported by grants from the US National Institutes of Health (P01 CA91955, K01 CA89267-02 and K07 CA89147-03) and from funds provided by the Commonwealth Universal Research Enhancement Program of the Pennsylvania Department of Health.

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Authors and Affiliations

  1. The Wistar Institute, 3601 Spruce St., Philadelphia, 19104, Pennsylvania, USA
    Carlo C Maley
  2. Division of Human Biology, Fred Hutchinson Cancer Research Center, P.O. Box 19024, Seattle, 98109, Washington, USA
    Patricia C Galipeau, Xiaohong Li, Carissa A Sanchez, Thomas G Paulson, Patricia L Blount, Peter S Rabinovitch & Brian J Reid
  3. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, P.O. Box 19024, Seattle, 98109, Washington, USA
    Patricia C Galipeau, Xiaohong Li, Carissa A Sanchez, Thomas G Paulson, Patricia L Blount, Peter S Rabinovitch & Brian J Reid
  4. Department of Pathology, University of Washington, Seattle, 98195, Washington, USA
    Jennifer C Finley, Rosa-Ana Risques & Peter S Rabinovitch
  5. Department of Medicine, University of Washington, Seattle, 98195, Washington, USA
    V Jon Wongsurawat, Patricia L Blount & Brian J Reid
  6. Department of Genome Sciences, University of Washington, Seattle, 98195, Washington, USA
    Brian J Reid

Authors

  1. Carlo C Maley
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  2. Patricia C Galipeau
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  3. Jennifer C Finley
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  4. V Jon Wongsurawat
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  5. Xiaohong Li
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  6. Carissa A Sanchez
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  7. Thomas G Paulson
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  8. Patricia L Blount
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  9. Rosa-Ana Risques
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  10. Peter S Rabinovitch
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  11. Brian J Reid
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Correspondence toCarlo C Maley.

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Maley, C., Galipeau, P., Finley, J. et al. Genetic clonal diversity predicts progression to esophageal adenocarcinoma.Nat Genet 38, 468–473 (2006). https://doi.org/10.1038/ng1768

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