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Letter
Nature Genetics  33, 49 - 54 (2002)
Published online: 9 December 2002; | doi:10.1038/ng1060

A molecular signature of metastasis in primary solid tumors

Sridhar Ramaswamy1, 2, Ken N. Ross1, Eric S. Lander1, 3 & Todd R. Golub1, 2

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

2  Dana-Farber Cancer Institute/Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.

3  Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

Correspondence should be addressed to Sridhar Ramaswamy sridhar@genome.wi.mit.edu or Todd R. Golub golub@genome.wi.mit.edu
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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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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