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Genomic Alterations Indicate Tumor Origin and Varied Metastatic Potential of Disseminated Cells from Prostate Cancer Patients

¹ Division of Human Biology, ² Division of Public Health Sciences, and ³ Genomics Resource, Fred Hutchinson Cancer Research Center; Departments of ⁴ Urology and ⁵ Pathology, University of Washington, Seattle, Washington

Requests for reprints: Barbara J. Trask, Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Mail Stop C3-168, P. O. Box 19024, Seattle, WA 98109. Phone: 206-667-1470; Fax: 206-667-4023; E-mail: btrask{at}fhcrc.org or Robert L. Vessella, Department of Urology, University of Washington, Box 356510, University of Washington Medical Center, 1959 Northeast Pacific Street, Seattle, WA 98195. E-mail: vessella{at}u.washington.edu.

Key Words: Disseminated tumor cells • disseminated cells • prostate cancer • array CGH • genomic alterations

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 (DTC). We also show 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 for 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. [Cancer Res 2008;68(14):5599–608]

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