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The germline and somatic origins of prostate cancer heterogeneity

Yamaguchi, T. N.
; 
Houlahan, K. E.
; 
Zhu, H.
; 
Kurganovs, N.
; 
Livingstone, J.
; 
Fox, N. S.
; 
Yuan, J.
; 
Sietsma Penington, J.
; 
Jung, C. H.
; 
Schwarz, T.
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Abstract
This study uncovered 223 recurrently mutated driver regions using the largest cohort of prostate tumors to date. It reveals associations between germline SNPs, somatic drivers, and tumor aggression, offering significant insights into how prostate tumor evolution is shaped by germline factors and the timing of somatic mutations.
Authors
Yamaguchi, T. N.
Houlahan, K. E.
Zhu, H.
Kurganovs, N.
Livingstone, J.
Fox, N. S.
Yuan, J.
Sietsma Penington, J.
Jung, C. H.
Schwarz, T.
Jaratlerdsiri, W.
van Riet, J.
Georgeson, P.
Mangiola, S.
Taraszka, K.
Lesurf, R.
Jiang, J.
Chow, K.
Heisler, L. E.
Shiah, Y. J.
Ramanand, S. G.
Clarkson, M. J.
Nguyen, A.
Espiritu, S. M. G.
Stuchbery, R.
Jovelin, R.
Huang, V.
Bell, C.
O'Connor, E.
McCoy, P. J.
Lalansingh, C. M.
Cmero, M.
Salcedo, A.
Chan, E. K. F.
Liu, L. Y.
Stricker, P. D.
Bhandari, V.
Bornman, R. M. S.
Sendorek, D. H. S.
Lonie, A.
Prokopec, S. D.
Fraser, M.
Peters, J. S.
Foucal, A.
Mutambirwa, S. B. A.
McIntosh, L.
Orain, M.
Wakefield, M.
Picard, V.
Park, D. J.
Hovington, H.
Kerger, M.
Bergeron, A.
Sabelnykova, V.
Seo, J. H.
Pomerantz, M. M.
Zaitlen, N.
Waszak, S. M.
Gusev, A.
Lacombe, L.
Fradet, Y.
Ryan, A.
Kishan, A. U.
Lolkema, M. P.
Weischenfeldt, J.
Têtu, B.
Costello, A. J.
Hayes, V. M.
Hung, R. J.
He, H. H.
McPherson, J. D.
Pasaniuc, B.
van der Kwast, T.
Papenfuss, A. T.
Freedman, M. L.
Pope, B. J.
Bristow, R. G.
Mani, R. S.
Corcoran, N. M.
Reimand, J.
Hovens, C. M.
Boutros, P. C.
Affiliation
Ontario Institute for Cancer Research, Toronto, Canada. Department of Human Genetics, University of California, Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, Los Angeles, California. Institute for Precision Health, University of California, Los Angeles, Los Angeles, California. Department of Medical Biophysics, University of Toronto, Toronto, Canada. Vector Institute, Toronto, Canada. Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. Australian Prostate Cancer Research Centre Epworth, Richmond, Australia. Department of Surgery, The University of Melbourne, Parkville, Australia. Department of Pathology, UT Southwestern Medical Center, Dallas, Texas. Bioinformatics Division, Walter and Eliza Hall Institute, Parkville, Australia. Melbourne Bioinformatics, The University of Melbourne, Melbourne, Australia. Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, California. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California. Laboratory for Human Comparative and Prostate Cancer Genomics, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, Australia. Department of Medical Oncology, Erasmus University, Rotterdam, the Netherlands. Department of Computer Science, University of California, Los Angeles, Los Angeles, California. Laboratory for Human Comparative and Prostate Cancer Genomics, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Darlinghurst, Australia. Division of Urology, Royal Melbourne Hospital, Parkville, Australia. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. St Vincent's Clinical School, University of New South Wales, Randwick, Australia. Department of Urology, St. Vincent's Hospital Sydney, Darlinghurst, Australia. School of Health Systems and Public Health, University of Pretoria, Pretoria, South Africa. Department of Urology, Sefako Makgatho Health Science University, Medunsa, South Africa. Research Centre of CHU de Québec-Université Laval, Québec City, Canada. Division of Urology and Research Centre of CHU de Québec-Université Laval, Québec City, Canada. Department of Neurology, University of California, Los Angeles, Los Angeles, California. Department of Computational Medicine, University of California, Los Angeles, Los Angeles, California. Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway. Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts. Division of Genetics, Brigham Women's Hospital and Harvard Medical School, Boston, Massachusetts. The Eli and Edythe L. Broad Institute, Cambridge, Massachusetts. TissuPath Specialist Pathology Services, Mount Waverley, Australia. Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California. Center for Personalized Cancer Treatment, Rotterdam, the Netherlands. Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark. Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark. Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany. Central Clinical School, University of Sydney, Camperdown, Australia. Department of Medical Sciences, University of Limpopo, Mankweng, South Africa. Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada. Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. Department of Medical Biology, University of Melbourne, Parkville, Australia. Department of Mathematics and Statistics, University of Melbourne, Parkville, Australia. Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Australia. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia. Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Clinical Pathology, The University of Melbourne, Parkville, Australia. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia. Department of Medicine, Monash University, Clayton, Australia. Manchester Cancer Research Centre, Manchester, United Kingdom. Department of Urology, UT Southwestern Medical Center, Dallas, Texas. Department of Urology, Peninsula Health, Frankston, Australia. The Victorian Comprehensive Cancer Centre, Parkville, Australia. Department of Urology, University of California, Los Angeles, Los Angeles, California.
Description
Date
2025
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All Paterson Institute for Cancer Research
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Yamaguchi TN, Houlahan KE, Zhu H, Kurganovs N, Livingstone J, Fox NS, et al. The Germline and Somatic Origins of Prostate Cancer Heterogeneity. Cancer discovery. 2025 May 2;15(5):988-1017. PubMed PMID: 39945744. Pubmed Central PMCID: PMC12046336 study. R.M.S. Bornman reports grants from the Department of Defense during the conduct of the study. M. Fraser reports a patent for “Methods and systems for prostate cancer characterization and treatment” pending to University Health Network and a patent for “Multi-modal prostate cancer marker” issued to University Health Network. M. Wakefield reports grants from Stanford Fox Mediacal Research Foundation during the conduct of the study, as well as nonfinancial support from Clovis Oncology and AstraZeneca outside the submitted work. A.U. Kishan reports honorarium and research support from Varian Medical Systems, Lantheus, Point Biopharma, and Janssen, honorarium from Boston Scientific and Novartis, research support from Artera, and grant support from the Department of Defense and NIH. M.P. Lolkema reports personal fees from Roche and Amgen, grants and personal fees from Sanofi, JnJ, MSD, and grants from KWF (Dutch Cancer Foundation) and NWO (Dutch Governmental Science Fund) during the conduct of the study. M.L. Freedman reports personal fees from Precede Biosciences outside the submitted work. N.M. Corcoran reports grants and personal fees from AstraZeneca and Bayer, personal fees from Astellas, and nonfinancial support from SillaJen outside the submitted work. P.C. Boutros reports grants from Prostate Cancer Canada, the Canadian Cancer Society, the Canadian Institutes for Health Research, the Prostate Cancer Foundation, the Department of Defense PCRP, and the NIH/NCI during the conduct of the study, as well as other support from BioSymetrics Inc., Intersect Diagnostics Inc., and Sage Bionetworks outside the submitted work; in addition, P.C. Boutros has multiple issued and pending patents on prostate cancer biomarkers. No disclosures were reported by the other authors. Epub 2025/02/13. eng.
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https://christie.openrepository.com/handle/10541/628167
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