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A molecular signature of metastasis in primary solid tumors

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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Figure 1: Genes associated with metastases.
Figure 2: Hierarchical clustering and Kaplan–Meier survival analysis in lung adenocarcinoma.
Figure 3: Broad diagnostic utility of the signature associated with metastasis in solid tumors.

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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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Correspondence to Sridhar Ramaswamy or Todd R. Golub.

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The authors declare no competing financial interests.

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Ramaswamy, S., Ross, K., Lander, E. et al. A molecular signature of metastasis in primary solid tumors. Nat Genet 33, 49–54 (2003). https://doi.org/10.1038/ng1060

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