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Evidence for a Molecular Signature of Metastasis in Primary Solid Tumors

Project

Metastasis

Additional Projects/
Categories

Bioinformatics & Computational Biology

Abstract

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.

Authors

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

Publication Date

12/09/2002

Contact emails

sridhar@genome.wi.mit.edu

Publication URL

http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v33/n1/full/ng1060.html&filetype=PDF

Citation

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

Keywords

Metastasis; Computational Biology; Cancer

Supplemental Information

URLs

Name	URL
Multi-tumor Cancer Map Paper	http://www.pnas.org/cgi/content/full/98/26/15149
Lung Paper	http://www.pnas.org/cgi/content/full/98/24/13790
Breast Paper	http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v415/n6871/abs/415530a_fs.html&dynoptions=doi1027022117
Prostate Paper	http://www.cancercell.org/cgi/content/full/1/2/203/
Medulloblastoma Paper	http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v415/n6870/abs/415436a_fs.html&dynoptions=doi1027021898
Lymphoma Paper	http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v8/n1/abs/nm0102-68.html&dynoptions=doi1027021859

Files

Description	File
Manuscript	Metastases_Nature_Genetics_030131_ng1060.pdf
Supplement	Mets_Supplement_Revised_Final_110802_SR.pdf
Supplemental Information	Mets_Supplement_Information_041110_KR.xls
Dataset A - Global Cancer Map Tumor vs. Met.	DatasetA_Tum_vs_Met.res
Dataset B - Lung Outcome	DatasetB_Lung_outcome.res
Dataset C - Rosetta Breast Outcome	DatasetC_Rosetta_breast_outcome.res
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