Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories.

Autor:	Gerhauser C; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Favero F; Finsen Laboratory, Rigshospitalet, DK-2200, Copenhagen, Denmark; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, DK-2200, Copenhagen, Denmark., Risch T; Max Planck Institute for Molecular Genetics, Otto Warburg Laboratory Gene Regulation and Systems Biology of Cancer, Ihnestrasse 63-73, 14195 Berlin, Germany., Simon R; Department of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Feuerbach L; Division Applied Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Assenov Y; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Heckmann D; Division of Cancer Genome Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Sidiropoulos N; Finsen Laboratory, Rigshospitalet, DK-2200, Copenhagen, Denmark; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, DK-2200, Copenhagen, Denmark., Waszak SM; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69120 Heidelberg, Germany., Hübschmann D; Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Department for Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology and Bioquant, University of Heidelberg, Heidelberg 69120, Germany; Department of Pediatric Immunology, Hematology and Oncology, University Hospital, Heidelberg 69120, Germany., Urbanucci A; Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, Forskningsparken, University of Oslo, 0316 Oslo, Norway; Institute for Cancer Genetics and Informatics, Oslo University Hospital, 0316 Oslo, Norway; Department of Core Facilities, Institute for Cancer Research, Oslo University Hospital, 0316 Oslo, Norway., Girma EG; Finsen Laboratory, Rigshospitalet, DK-2200, Copenhagen, Denmark; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, DK-2200, Copenhagen, Denmark., Kuryshev V; Division of Cancer Genome Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Klimczak LJ; Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Durham, 27709 NC, USA., Saini N; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, 27709 NC, USA., Stütz AM; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69120 Heidelberg, Germany., Weichenhan D; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Böttcher LM; Department of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Toth R; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Hendriksen JD; Finsen Laboratory, Rigshospitalet, DK-2200, Copenhagen, Denmark; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, DK-2200, Copenhagen, Denmark., Koop C; Department of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Lutsik P; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Matzk S; Max Planck Institute for Molecular Genetics, Otto Warburg Laboratory Gene Regulation and Systems Biology of Cancer, Ihnestrasse 63-73, 14195 Berlin, Germany., Warnatz HJ; Max Planck Institute for Molecular Genetics, Otto Warburg Laboratory Gene Regulation and Systems Biology of Cancer, Ihnestrasse 63-73, 14195 Berlin, Germany., Amstislavskiy V; Max Planck Institute for Molecular Genetics, Otto Warburg Laboratory Gene Regulation and Systems Biology of Cancer, Ihnestrasse 63-73, 14195 Berlin, Germany., Feuerstein C; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany., Raeder B; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69120 Heidelberg, Germany., Bogatyrova O; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Schmitz EM; PROGETHER Prostate Cancer Network, 0316 Oslo, Norway., Hube-Magg C; Department of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Kluth M; Department of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Huland H; Martini-Clinic Prostate Cancer Center at the University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany., Graefen M; Martini-Clinic Prostate Cancer Center at the University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany., Lawerenz C; Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Henry GH; Department of Urology, UT Southwestern Medical Center, Dallas, TX 75390-9110, USA., Yamaguchi TN; Informatics & Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Canada., Malewska A; Department of Urology, UT Southwestern Medical Center, Dallas, TX 75390-9110, USA., Meiners J; Department of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Schilling D; Division of Cancer Genome Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; NCT Trial Center, National Center for Tumor Diseases and German Cancer Research Center, 69120 Heidelberg, Germany., Reisinger E; Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Eils R; Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Department for Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology and Bioquant, University of Heidelberg, Heidelberg 69120, Germany., Schlesner M; Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Bioinformatics and Omics Data Analytics (B240), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany., Strand DW; Department of Urology, UT Southwestern Medical Center, Dallas, TX 75390-9110, USA., Bristow RG; Manchester Cancer Research Centre, University of Manchester, 555 Wilmslow Road, Manchester, UK., Boutros PC; Ontario Institute for Cancer Research, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada., von Kalle C; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Division of Translational Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Gordenin D; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, 27709 NC, USA., Sültmann H; Division of Cancer Genome Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Brors B; Division Applied Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Sauter G; Department of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Plass C; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Yaspo ML; Max Planck Institute for Molecular Genetics, Otto Warburg Laboratory Gene Regulation and Systems Biology of Cancer, Ihnestrasse 63-73, 14195 Berlin, Germany., Korbel JO; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69120 Heidelberg, Germany. Electronic address: korbel@embl.de., Schlomm T; Martini-Clinic Prostate Cancer Center at the University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany; Charité Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany. Electronic address: thorsten.schlomm@charite.de., Weischenfeldt J; Finsen Laboratory, Rigshospitalet, DK-2200, Copenhagen, Denmark; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, DK-2200, Copenhagen, Denmark; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69120 Heidelberg, Germany; Charité Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany. Electronic address: joachim.weischenfeldt@bric.ku.dk.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2018 Dec 10; Vol. 34 (6), pp. 996-1011.e8.
DOI:	10.1016/j.ccell.2018.10.016
Abstrakt:	Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ≤55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors. Finally, we combined the patterns of molecular co-occurrence and risk-based subgroup information to deconvolve the molecular and clinical trajectories of prostate cancer from single patient samples. (Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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