Abstract 4308: 3D nuclear telomeric signatures define circulating tumor cells (CTCs) and characterize CTC subpopulations in intermediate risk prostate cancer patients

Abstract

Intermediate risk prostate cancer is a current medical challenge since the patients in this group can either be stable or progress, and there is no predictor for individual risk. Stratifying these patients would spare the patients unnecessary treatment or indicate the start of treatment immediately without losing precious time. Currently, prostate specific antigen (PSA) is used as evidence for biochemical progression. A more sensitive biomarker is needed to detect disease progression earlier and more reliably. We have isolated circulating tumor cells (CTCs) using a filtration-based device (ScreenCell). We subsequently performed the genetic characterization of the captured CTCs on a single cell basis. Using three-dimensional (3D) nuclear telomere imaging and quantitative analysis of 3D telomeric signatures of CTCs, we have characterized CTCs in the blood of the patients and have identified patient subgroups with one or more groups of CTCs. 380 samples of intermediate risk prostate cancer all revealed the presence of CTCs. However, the CTCs found were not genetically identical. Marked heterogeneity was seen, and three main groups of CTC profiles were defined based on TeloView software our group developed earlier. Repeat samples taken 6 months intervals define stable, mildly changing and significantly altered 3D profiles indicative of disease stability vs. progression. Citation Format: Awe A. Julius, Adam Yan, Nidhi Shah, Klewes Ludger, Alexandra Kuzyk, Michael Xu, Ramy Boles, Jeff Saranchuk, Darrel Drachenberg, Sabine Mai. 3D nuclear telomeric signatures define circulating tumor cells (CTCs) and characterize CTC subpopulations in intermediate risk prostate cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4308. doi:10.1158/1538-7445.AM2014-4308

Genomic Instability in Circulating Tumor Cells

“…CTCs from prostate patients, breast cancer, and melanoma tend to have more telomere aggregates, while CTCs from colon and lung cancer have a significant increase in the number of telomeres [ 99 ]. Other studies have indicated that telomere signatures can change over time and during treatment, suggesting marked heterogeneity [ 13 , 100 ]. Julius et al (2014) collected repeated samples within six-month intervals defined as stable, mildly changing, and significantly altered 3D profiles indicative of disease stability versus progression [ 100 ].…”

“…Other studies have indicated that telomere signatures can change over time and during treatment, suggesting marked heterogeneity [ 13 , 100 ]. Julius et al (2014) collected repeated samples within six-month intervals defined as stable, mildly changing, and significantly altered 3D profiles indicative of disease stability versus progression [ 100 ]. Most recently, Drachenberg et al (2019) and Wark et al (2019) assessed the individual pretreatment risk of progression in intermediate-risk and high-risk prostate cancer patients undergoing radiation and hormone deprivation therapies, respectively [ 101 , 102 ].…”

“…CTCs from prostate patients, breast cancer, and melanoma tend to have more telomere aggregates, while CTCs from colon and lung cancer have a significant increase in the number of telomeres [99]. Other studies have indicated that telomere signatures can change over time and during treatment, suggesting marked heterogeneity [13,100] [101,102]. They identified disease heterogeneity among a clinically homogeneous group of prostate cancer patients.…”