The genomic landscape of unsuspected, incidentally detected Gleason 7 prostate cancer found on autopsy

摘要: Introduction & Objectives Changes in our way of thinking in medicine are sometimes driven by observations in a small number of patients. For instance, when whole-genome sequencing used to track the lethal cell clone in a single patient who died of prostate cancer (PCa), surprisingly, revealed that it arose from a small, low-grade PCa focus. The genomic landscape of unsuspected, incidentally detected PCa on autopsy in men never found with the disease during their lifetime is virtually unknown. Intriguingly, while the field has anticipated that most autopsy-detected PCa are of low tumor volume and low Gleason score (GS), we and others have shown that nearly 25% of unsuspected autopsy detected PCa in Caucasian men were GS≥7. Materials & Methods We used prostate glands prospectively collected during autopsy from Caucasian men, deceased with no known history of PCa, accrued by the University of Moscow, Russia and analyzed in Toronto, Canada. We limited the scope of our study to unifocal GS7 tumors with good DNA quantity and quality. DNA was isolated from the autopsy-detected tumors using QIAamp DNA Mini Kit (Hilden, Germany). To profile genome-wide copy number aberrations (CNAs), we used the OncoScan® FFPE Express v3 platform, optimized for highly degraded samples. BioDiscovery Nexus Express TM for OncoScan 3 was used to call CNAs using the SNP-FASST2 algorithm. We compared autopsy CNA data to intermediate-risk prostate cancer cases from the Canadian Prostate Cancer Genome Network (CPC-GENE project), all of whom underwent radiotherapy or radical prostatectomy for localized, non …