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Genetic background is an important determinant of metastatic potential

Nature Genetics volume 34, pages 23–24 (2003)Cite this article

Recently there has been some debate about the etiology of cancer metastatic potential. Using microarray gene expression patterns of breast carcinomas, van't Veer et al.1 reported that a set of 117 genes predicted metastatic potential. More recently, a small set of 17 genes was reported to predict metastatic potential for a variety of solid tumors2. These findings suggest that most primary tumor cells express a 'metastasis signature', in contrast to the classic model, which predicts that only a rare subpopulation of primary tumor cells have accumulated the numerous alterations required for metastasis. Based on this evidence, Bernards and Weinberg3 recently posited that combinations of early oncogenic alterations, not specific events that promote metastasis, determine metastatic potential. This hypothesis might explain why metastasis occurs in some individuals with small, localized tumors (that is, tumors whose cell number is too small to have statistical likelihood of accumulating adequate numbers of mutations proposed in the conventional model).

In contrast, there is persuasive evidence for the existence of mutations that promote metastasis. For example, metastasis-specific loss of heterozygosity has been associated with many solid tumors. Based on the tumor-suppressor paradigm, several laboratories have cloned genes that, when reintroduced into tumor cells, suppress the formation of secondary tumors without altering primary tumor initiation or kinetics. So far, eight metastasis-suppressor genes have been described (reviewed in ref. 4).

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Authors and Affiliations

  1. Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Building 41, Room D702, 41 Library Drive, Bethesda, 20892-5060, Maryland, USA

    Kent Hunter

  2. Department of Pathology and Comprehensive Cancer Center, University of Alabama at Birmingham, 1670 University Blvd., Volker Hall G-038, Birmingham, 35294-0019, Alabama, USA

    Danny R. Welch

  3. Genome Institute of Singapore, 1 Science Park Road, The Capricorn #05-01, Science Park II, 117528, Singapore

    Edison T. Liu

Authors
  1. Kent Hunter
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  2. Danny R. Welch
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  3. Edison T. Liu
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Correspondence to Kent Hunter.

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Hunter, K., Welch, D. & Liu, E. Genetic background is an important determinant of metastatic potential. Nat Genet 34, 23–24 (2003). https://doi.org/10.1038/ng0503-23b

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