MP35-13 WHITE BLOOD CELLS FROM PROSTATE CANCER PATIENTS CARRY DISTINCT CHROMOSOME CONFORMATIONS
INTRODUCTION AND OBJECTIVES
Current diagnostic blood tests for prostate cancer (PCa) are unreliable for the early stage disease, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance of negative biopsies in men with prostate cancer. In comparison to the imaging biomarker MRI, which identifies established and significant prostate cancer we investigate early epigenetic changes as a diagnostic biomarker. Three-dimensional genome architecture and chromosome structures undergo changes early during tumourigenesis both in tumour and in circulating cells and can be potentially used for cancer diagnosis.
In this report, we have performed chromosome conformation screening for 14,240 chromosomal loops in the loci of 425 cancer related genes in peripheral blood mononuclear cells (PBMCs) of n=107 PCa patients and n=105 non-cancer controls. The cancer cohort consisted of all D'Amico risk groups including metastatic disease.
Our data show that PBMCs from PCa patients acquire specific chromosome conformation changes in the loci of cancer-related genes. New chromosomal loops in the loci of CASP2, ETS1, SLC22A3, MAP3K14 genes were unique to the PCa cohort. Similar chromosomal conformations were identified in primary prostate tumours from these patients, but not in normal prostate tissues. Blind testing on a validation cohort of n=10 pts and n=10 controls yielded PCa detection with 80% sensitivity and 80% specificity. Surprisingly, utilising the signature to predict D'Amico low risk v high risk disease was also highly accurate (Sensitivity 84%, Specificity 89%).
We have identified a subset of blood chromosomal conformations that are strongly indicative of PCa presence and possibly risk of advanced disease. These signatures have a significant potential for development of a quick diagnostic blood test for prostate cancer or as staging adjunct.