Multiregion sampling of de novo metastatic prostate cancer reveals complex polyclonality and augments clinical genotyping.

Autor: Warner EW; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Van der Eecken K; Department of Pathology, Ghent University Hospital, Ghent, Belgium.; Department of Human Structure and Repair, Ghent University, Ghent, Belgium., Murtha AJ; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Kwan EM; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.; Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia., Herberts C; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Sipola J; Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland., Ng SWS; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Chen XE; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Fonseca NM; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Ritch E; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Schönlau E; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Bernales CQ; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Donnellan G; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Munzur AD; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Parekh K; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Beja K; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Wong A; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Verbeke S; Department of Pathology, Ghent University Hospital, Ghent, Belgium., Lumen N; Department of Human Structure and Repair, Ghent University, Ghent, Belgium., Van Dorpe J; Department of Pathology, Ghent University Hospital, Ghent, Belgium., De Laere B; Department of Human Structure and Repair, Ghent University, Ghent, Belgium., Annala M; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.; Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland., Vandekerkhove G; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada., Ost P; Department of Human Structure and Repair, Ghent University, Ghent, Belgium., Wyatt AW; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada. awwyatt@mail.ubc.ca.; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada. awwyatt@mail.ubc.ca.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2024 Jan; Vol. 5 (1), pp. 114-130. Date of Electronic Publication: 2024 Jan 04.
DOI: 10.1038/s43018-023-00692-y
Abstrakt: De novo metastatic prostate cancer is highly aggressive, but the paucity of routinely collected tissue has hindered genomic stratification and precision oncology. Here, we leveraged a rare study of surgical intervention in 43 de novo metastatic prostate cancers to assess somatic genotypes across 607 synchronous primary and metastatic tissue regions plus circulating tumor DNA. Intra-prostate heterogeneity was pervasive and impacted clinically relevant genes, resulting in discordant genotypes between select primary restricted regions and synchronous metastases. Additional complexity was driven by polyclonal metastatic seeding from phylogenetically related primary populations. When simulating clinical practice relying on a single tissue region, genomic heterogeneity plus variable tumor fraction across samples caused inaccurate genotyping of dominant disease; however, pooling extracted DNA from multiple biopsy cores before sequencing can rescue misassigned somatic genotypes. Our results define the relationship between synchronous treatment-sensitive primary and metastatic lesions in men with de novo metastatic prostate cancer and provide a framework for implementing genomics-guided patient management.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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