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A molecular signature of metastasis in primary solid tumors

Nature Genetics volume 33, pages 4954 (2003) | Download Citation

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Abstract

Metastasis is the principal event leading to death in individuals with cancer, yet its molecular basis is poorly understood1. To explore the molecular differences between human primary tumors and metastases, we compared the gene-expression profiles of adenocarcinoma metastases of multiple tumor types to unmatched primary adenocarcinomas. We found a gene-expression signature that distinguished primary from metastatic adenocarcinomas. More notably, we found that a subset of primary tumors resembled metastatic tumors with respect to this gene-expression signature. We confirmed this finding by applying the expression signature to data on 279 primary solid tumors of diverse types. We found that solid tumors carrying the gene-expression signature were most likely to be associated with metastasis and poor clinical outcome (P < 0.03). These results suggest that the metastatic potential of human tumors is encoded in the bulk of a primary tumor, thus challenging the notion that metastases arise from rare cells within a primary tumor that have the ability to metastasize2.

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Acknowledgements

We thank R. A. Weinberg, P. Tamayo and M. A. Gillette for helpful comments. This work was supported in part by a grant from the US National Institutes of Health to T.R.G.

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Affiliations

  1. Whitehead Institute/MIT Center for Genome Research, One Kendall Square, Building 300, Cambridge, Massachusetts 02139, USA.

    • Sridhar Ramaswamy
    • , Ken N. Ross
    • , Eric S. Lander
    •  & Todd R. Golub
  2. Dana-Farber Cancer Institute/Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.

    • Sridhar Ramaswamy
    •  & Todd R. Golub
  3. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Eric S. Lander

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Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Sridhar Ramaswamy or Todd R. Golub.

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DOI

https://doi.org/10.1038/ng1060