title: Genomic alterations indicate tumor origin and varied metastatic potential of disseminated cells from prostate cancer patients.
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 (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.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Ilona N
authors.initials: IN
authors.lastname: Holcomb
authors.forename: Douglas I
authors.initials: DI
authors.lastname: Grove
authors.forename: Martin
authors.initials: M
authors.lastname: Kinnunen
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Friedman
authors.forename: Ian S
authors.initials: IS
authors.lastname: Gallaher
authors.forename: Todd M
authors.initials: TM
authors.lastname: Morgan
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Sather
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Delrow
authors.forename: Peter S
authors.initials: PS
authors.lastname: Nelson
authors.forename: Paul H
authors.initials: PH
authors.lastname: Lange
authors.forename: William J
authors.initials: WJ
authors.lastname: Ellis
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: True
authors.forename: Janet M
authors.initials: JM
authors.lastname: Young
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Trask
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009693:Nucleic Acid Hybridization; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*