Abstract 804: Disseminated tumor cell heterogeneity and dormancy in prostate cancer.

Abstract

Abstract Prostate cancer (PCa) can remain in the bone marrow for a prolonged period of time (>5 years) while the patient shows no evidence of disease before the cancer eventually recurs. Dormant cancer cells can be detected in bone, the principal metastatic site of PCa, and these bone-homing cancer cells are known as disseminated tumor cells (DTC). Little information is available on the heterogeneity and dormancy of DTC in PCa. In this study, we isolated and compared the gene expression profile of individual DTC (n=45) from the bone marrow of 4 PCa patients with no evidence of disease and 5 patients with advanced disease. Using principle component analysis and cluster analysis of the 1000 most variable genes, we determined the heterogeneity of the DTC population within each patient. To identify a dormancy signature from DTC in the bone marrow and primary PCa cells, we carried out two gene expression analyses: DTC in patients with no evidence of disease vs. those with advanced disease, and primary PCa tissues from patients with a short vs. long dormancy period post radical prostatectomy (8-86 months). Genes associated in other cancers with cellular senescence, cell-cycle inhibition, and dormancy were analyzed. Candidate genes from both gene expression arrays were validated at the protein level by a tissue microarray consisting of 64 primary PCa cases that recurred after either a short or long dormancy period post radical prostatectomy (6-121 months). The identification of heterogeneous gene signatures in DTC and novel proteins that promote dormancy will guide the development of possible biomarkers and therapeutic targets to prevent PCa recurrence, possibly by either eliminating DTC or inhibiting their escape from dormancy. Citation Format: Hung-Ming Lam, Lisly Chéry, Ilsa Coleman, Bryce Lakely, Sandy Larson, Roger Coleman, Lisha Brown, Kathy Doan, Jennifer Noteboom, Xiaotun Zhang, Lawrence True, Peter Nelson, Bruce Montgomery, Paul Lange, Linda Snyder, Robert Vessella, Colm Morrissey. Disseminated tumor cell heterogeneity and dormancy in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 804. doi:10.1158/1538-7445.AM2013-804