PO-356 White blood cells from prostate cancer patients carry distinct chromosome conformations

Abstract

IntroductionCurrent diagnostic blood tests for prostate cancer 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. Three-dimensional genome architecture and chromosome structures undergo early changes during tumourigenesis both in tumour and in circulating cells and can be potentially used for cancer diagnosis.Material and methodsIn 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 prostate cancer patients (n=107) and non-cancer controls (n=105).Results and discussionsOur data show that PBMCs from prostate cancer 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 prostate cancer cohort. In prostate cancer patients, chromosome conformations identified in PBMCs had high similarity to those in primary prostate tumours. Blind testing on an independent validation cohort of prostate cancer patients yielded prostate cancer detection with 80% sensitivity and 80% specificity.ConclusionOur results indicate that there are specific chromosome conformations in the blood of prostate cancer patients that are not present in control group. These conformations are shared between PBMCs and primary tumours, but exact mechanism of their appearance is not yet identified. It is possible that these epigenetic signatures may potentially lead to development of a blood-based prostate cancer diagnostic tests. Similar approaches could be used to investigate the prognostic significance of these signatures to determine the risk of tumour progression.