Characterization of a centrosme loss - induced tumorigenic signature in prostate epithelial cells

Unlike many cancers, prostate cacner (PCa) lacks hallmark mutations in key oncogenes and tumor-suppressorgenes. Instead, PCa exhibit extensive genomic rearrangements and chromosomal instability (CIN). Previously, we found that cell within early-grade human primary prostate adenocarcinomas (PRAD) frequently lack centrosomes, and this frequency correlates with tumor grade. We demonstrated that transient removal of centrosomes within non-tumorigenic human prostate epithelial cells (hPrEC) induces CIN and was, strikingly, sufficient to transform subpopulations of cells capable of producing xenograft tumors in mice. To unravel the molecular mechanisms underlying this path to tumorigenesis, we isolated DNA from parental hPrECs, clonal lines subjected to transient centrosome loss, and xenograft tumor cells and performed bulk-whole genome sequencing. This allowed us to characterize the genomic profile induced by centrosome loss.