Genomic Profiling of Rare Disseminated Tumor Cells from Prostate Cancer

Publication Type:

Journal Article

Source:

Cytogenetic and Genome Research, Volume 136, Number 4, p.337-337 (2012)

Keywords:

2012, Clinical Research Division, Clinical Research Division Human Biology Division Public Health Sciences Division May 2014 2014Q2 CCSG, Human Biology Division, May 2014, Public Health Sciences Division

Abstract:

Prostate tumor cell dissemination remains a critical challenge in understanding disease progression and effective long-term treatment of patients. Disseminated tumor cells (DTCs) from bone marrow are resistant to chemotherapy and radiation, representing a potential long-lived source for lethal metastases. Very limited knowledge exists about the biology of these rare cells, including the genomic aberrations associated with clinical outcome. We enriched DTCs from bone marrow aspirates and individually captured them under the microscope. Whole genome amplification (WGA) and high-density SNP-arrays were used to genomically profile rare DTC populations (n = 2–25 cells). We quantified and characterized copy number alterations (CNAs) and loss-of-heterozygosity (LOH) regions in samples isolated from 58 patients taken at the time of radical prostatectomy and from 13 patients with advanced, metastatic or lethal prostate cancer. DTC aberrations were classified by tumor stage and compared to those abnormalities identified in primary and metastatic tumors. Regions of interest were validated with real-time PCR. Extensive optimization of analysis parameters were employed to handle the increased probe variation associated with low input DNA quantity and WGA. DTCs isolated at the time of radical prostatectomy from earlystage cancer patients are generally heterogeneous and marked with limited focal aberrations, including deletions of less than 100 kb and, less frequently, gains of less than 500 kb. A considerable number of these CNAs are rare and unique to DTCs. Cancerspecific alterations involve genes of the cadherin family and transcription factors SIX3 and SOX4 . Most aberrations are patientspecific and may alter common biological pathways. In contrast, DTCs from patients with advanced-stage prostate cancer typically show frequent and large ( 1 1 Mb) clonal amplifications and deletions, suggesting a high degree of genomic instability common among these patients. Further bioinformatic analysis is underway to gain understanding of the genomic events that drive DTC dissemination, dormancy, and metastatic reactivation in prostate cancer.

Notes:

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