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dc.contributor.authorFoucal, A.
dc.contributor.authorLivingstone, J.
dc.contributor.authorSalcedo, A.
dc.contributor.authorKuk, C.
dc.contributor.authorFraser, M.
dc.contributor.authorPushkar, D.
dc.contributor.authorGovorov, A.
dc.contributor.authorKovylina, M.
dc.contributor.authorBristow, Robert G
dc.contributor.authorFleshner, N. E.
dc.contributor.authorVan der Kwast, T. H.
dc.contributor.authorZlotta, A. R
dc.contributor.authorBoutros, P.
dc.date.accessioned2021-09-07T13:16:24Z
dc.date.available2021-09-07T13:16:24Z
dc.date.issued2021en
dc.identifier.citationFoucal A, Livingstone J, Salcedo A, Kuk C, Fraser M, Pushkar D, et al. The genomic landscape of unsuspected, incidentally detected Gleason 7 prostate cancer found on autopsy. European Urology. 2021;79:S1436-S.en
dc.identifier.urihttp://hdl.handle.net/10541/624565
dc.description.abstractIntroduction & 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-indolent GS6-7 disease. Results: Three autopsy incidentally detected tumors were analyzed (ages 63, 70, 80) and compared to 300 surgical and biopsy-specimens from CPC-GENE. Driver gene hits were common in autopsy specimens: deletions in TP53 were observed in all three, BRCA2 in two and RB1 loss in two. A TMPRSS2:ERG fusion, caused by a deletion of chr21:39988436-42859011, was observed in one sample. Two of the three autopsy samples were indistinguishable from the diagnosed tumors in the CPC-GENE set. A limitation of this study is that although the three GS 7 were found incidentally on autopsy, they were not necessarily indolent: These men could have died of something else before their PCa became diagnosed. Conclusions: To our surprise, this study has shown, to the best of our knowledge, for the first time that unsuspected PCa GS7 detected incidentally on autopsy is genomically indistinguishable from clinically detected tumors. Autopsy studies have revealed the presence of a large reservoir of PCa, including GS7, which exist in the population and do not cause clinical symptoms or death. Most GS7 tumors found on autopsy in this study, intriguingly displayed mutations usually observed in more aggressive forms of the disease. This may suggest that other factors such as epigenetics could play an important role.en
dc.language.isoenen
dc.titleThe genomic landscape of unsuspected, incidentally detected Gleason 7 prostate cancer found on autopsyen
dc.typeMeetings and Proceedingsen
dc.contributor.departmentOntario Institute for Cancer Research, Dept. of Informatics and Biocomputing, Toronto, Canadaen
dc.identifier.journalEuropean Urologyen
dc.description.noteen]


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