title: Dynamics of three-dimensional telomere profiles of circulating tumor cells in patients with high-risk prostate cancer who are undergoing androgen deprivation and radiation therapies.
abstract: Accurate assessment and monitoring of the therapeutic efficacy of locally advanced prostate cancer remains a major clinical challenge. Contrary to prostate biopsies, circulating tumor cells (CTCs) are a cellular source repeatedly obtainable by blood sampling and could serve as a surrogate marker for treatment efficacy. In this study, we used size-based filtration to isolate and enumerate CTCs from the blood of 20 patients with high-risk (any one of cT3, Gleason 8-10, or prostate-specific antigen>20ng/ml), nonmetastatic, and treatment-naive prostate cancer before and after androgen deprivation therapy (ADT) and radiation therapy (RT).
  
  
  
  We performed 3D telomere-specific quantitative fluorescence in situ hybridization on isolated CTCs to determine 3D telomere profiles for each patient before and throughout the course of both ADT and RT.
  
  
  
  Based on the distinct 3D telomere signatures of CTC before treatment, patients were divided into 3 groups. ADT and RT resulted in distinct changes in 3D telomere signatures of CTCs, which were unique for each of the 3 patient groups.
  
  
  
  The ability of 3D telomere analysis of CTCs to identify disease heterogeneity among a clinically homogeneous group of patients, which reveals differences in therapeutic responses, provides a new opportunity for better treatment monitoring and management of patients with high-risk prostate cancer.
authors.affiliation: Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Canada; Department of Human Anatomy and Cell Sciences, University of Manitoba, Winnipeg, Canada.
authors.forename: Landon
authors.initials: L
authors.lastname: Wark
authors.affiliation: Department of Human Anatomy and Cell Sciences, University of Manitoba, Winnipeg, Canada; Medical Microbiology and Infectious Diseases, Department of Oncology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klonisch
authors.affiliation: Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Canada; Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Systems Biology Research Centre, School of Life Sciences, University of Skovde, Skovde, Sweden.
authors.forename: Julius
authors.initials: J
authors.lastname: Awe
authors.affiliation: Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Canada.
authors.forename: Cecile
authors.initials: C
authors.lastname: LeClerc
authors.affiliation: Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Canada.
authors.forename: Brandon
authors.initials: B
authors.lastname: Dyck
authors.affiliation: Department of Oncology, University of Calgary, Calgary, Alberta, Canada; CancerCare Manitoba, Winnipeg, Manitoba, Canada; Tom Baker Cancer Centre, Calgary, Alberta, Canada. Electronic address: harvey.quon@albertahealthservices.ca.
authors.forename: Harvey
authors.initials: H
authors.lastname: Quon
authors.affiliation: Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Canada; Department of Human Anatomy and Cell Sciences, University of Manitoba, Winnipeg, Canada; Department of Oncology, University of Calgary, Calgary, Alberta, Canada. Electronic address: sabine.mai@umanitoba.ca.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mai
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D002452:Cell Count / Q000379:methods; D002467:Cell Nucleus / Q000378:metabolism; D059248:Chemoradiotherapy / Q000379:methods; D005260:Female; D042822:Genomic Instability / Q000187:drug effects* / Q000528:radiation effects; D064368:Healthy Volunteers; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007610:Kallikreins / Q000097:blood; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011944:Receptors, Androgen / Q000378:metabolism; D016615:Telomere / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D016896:Treatment Outcome
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Biomarkers; Circulating tumor cells; High-risk prostate cancer; Telomeres