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.

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.

Urologic oncology. 2016 Dec 09 [Epub ahead of print]

Landon Wark, Thomas Klonisch, Julius Awe, Cecile LeClerc, Brandon Dyck, Harvey Quon, Sabine Mai

Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Canada; Department of Human Anatomy and Cell Sciences, University of Manitoba, Winnipeg, Canada., 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., 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., Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Canada., Department of Oncology, University of Calgary, Calgary, Alberta, Canada; CancerCare Manitoba, Winnipeg, Manitoba, Canada; Tom Baker Cancer Centre, Calgary, Alberta, Canada. Electronic address: ., 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: .