Evidence for a Molecular Signature of Metastasis in Primary Solid Tumors

Nature Genetics, vol. 33, January 2003, pp. 49-54.. Published: 2002.12.08

Sridhar Ramaswamy, Ken N. Ross, Eric S. Lander, & Todd R. Golub

Read Manuscript


Metastasis is the principal cause of death in cancer patients, yet its genetic basis remains poorly understood. 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. First, we were able to find a gene expression signature that distinguished primary from metastatic adenocarcinomas. Second, and more surprisingly, we found that a subset of primary tumors resembled metastatic tumors with respect to this gene expression signature. We confirmed this finding by applying this expression signature to data on 279 primary solid tumors of diverse types. We found that solid tumors carrying the metastasis 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 metastasize.

Keywords: Cancer Computational Biology Metastasis

Supplemental Data

Description Link/Filename
Multi-tumor Cancer Map Paper http://www.pnas.org/cgi/content/full/98/26/15149
Manuscript Metastases_Nature_Genetics_030131_ng1060.pdf
Lung Paper http://www.pnas.org/cgi/content/full/98/24/13790
Supplement Mets_Supplement_Revised_Final_110802_SR.pdf
Breast Paper http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v415/n6871/abs/415530a_fs.html&dynoptions=doi1027022117
Supplemental Information Mets_Supplement_Information_041110_KR.xls
Prostate Paper http://www.cancercell.org/cgi/content/full/1/2/203/
Dataset A - Global Cancer Map Tumor vs. Met. DatasetA_Tum_vs_Met.res
Dataset B - Lung Outcome DatasetB_Lung_outcome.res
Medulloblastoma Paper http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v415/n6870/abs/415436a_fs.html&dynoptions=doi1027021898
Dataset C - Rosetta Breast Outcome DatasetC_Rosetta_breast_outcome.res
Lymphoma Paper http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v8/n1/abs/nm0102-68.html&dynoptions=doi1027021859
Dataset D - Prostate Outcome DatasetD_prostate_outcome.res
Dataset E - Medulloblastoma Outcome DatasetE_medulloblastoma_outcome.res
Dataset F - LBC Lymphoma Outcome DatasetF_lymphoma_outcome.res
Table of Contents Table_of_Contents.pdf