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Genomic alterations indicate tumor origin and varied metastatic potential of disseminated cells from prostate-cancer patients

Holcomb, Ilona N. and Grove, Douglas I. and Kinnunen, Martin and Friedman, Cynthia L. and Gallaher, Ian S. and Morgan, Todd M. and Sather, Cassandra L. and Delrow, Jeffrey J. and Nelson, Peter S. and Lange, Paul H. and Ellis, William J. and True, Lawrence D. and Young, Janet M. and Hsu, Li and Trask, Barbara J. and Vessella, Robert L. (2008) Genomic alterations indicate tumor origin and varied metastatic potential of disseminated cells from prostate-cancer patients. Cancer Research, 68. pp. 5599-5608. ISSN 1538-7445

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Article URL: http://cancerres.aacrjournals.org/cgi/content/abst...

Abstract

Disseminated epithelial cells can be isolated from the bone marrow of a far greater fraction of prostate-cancer patients than the fraction of patients who progress to metastatic disease. To provide a better understanding of these cells, we have characterized their genomic alterations. We first present an array comparative genomic hybridization method capable of detecting genomic changes in the small number of disseminated cells (10-20) that can typically be obtained from bone-marrow aspirates of prostate-cancer patients. We show multiple regions of copy-number change, including alterations common in prostate cancer, such as 8p loss, 8q gain, and gain encompassing the androgen-receptor gene on Xq, in the disseminated cell pools from 11 metastatic patients. We found fewer and less striking genomic alterations in the 48 pools of disseminated cells from patients with organ-confined disease. However, we identify changes shared by these samples with their corresponding primary tumors and prostate-cancer alterations reported in the literature, evidence that these cells, like those in advanced disease, are disseminated tumor cells (DTCs). We also demonstrate that DTCs from patients with advanced and localized disease share several abnormalities, including losses containing cell-adhesion genes and alterations reported to associate with progressive disease. These shared alterations might confer the capability to disseminate or establish secondary disease. Overall, the spectrum of genomic deviations is evidence for metastatic capacity in advanced-disease DTCs and variation in that capacity in DTCs from localized disease. Our analysis lays the foundation for elucidation of the relationship between DTC genomic alterations and progressive prostate cancer.

Item Type: Article
Additional Information: This article is freely available at the journal website via the URL above and in PubMed Central.
DOI: 10.1158/0008-5472.CAN-08-0812
PubMed ID: 18632612
NIHMSID: NIHMS57787
PMCID: PMC2613025
Grant Numbers: P50-CA97186-05, DAMD 17-03-2-0033, T32-HG00035, RO1-AG14358-09, P30-CA15704-31, RO1-DC004209-10, RO1-CA098415-04, RO1-CA95717-04, U24-CA80295-03
Keywords or MeSH Headings: MH - Cell Adhesion MH - Cell Line, Tumor MH - Chromosome Mapping MH - Disease Progression MH - Gene Expression Profiling MH - *Gene Expression Regulation, Neoplastic MH - *Genome MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Models, Biological MH - Neoplasm Metastasis MH - Nucleic Acid Hybridization MH - Prostatic Neoplasms/*genetics/*pathology
Subjects: Cellular and Organismal Processes > Genetic processes > Genomic instability
Diseases > Solid tumors > Prostate cancer
Depositing User: Library Staff
Date Deposited: 14 Aug 2008 21:58
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/6

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