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

Clarissa Gerhauser, Francesco Favero, Thomas Risch, Ronald Simon, Lars Feuerbach, Yassen Assenov, Doreen Heckmann, Nikos Sidiropoulos, Sebastian M Waszak, Daniel Hübschmann, Alfonso Urbanucci, Etsehiwot G Girma, Vladimir Kuryshev, Leszek J Klimczak, Natalie Saini, Adrian M Stütz, Dieter Weichenhan, Lisa-Marie Böttcher, Reka Toth, Josephine D HendriksenChristina Koop, Pavlo Lutsik, Sören Matzk, Hans-Jörg Warnatz, Vyacheslav Amstislavskiy, Clarissa Feuerstein, Benjamin Raeder, Olga Bogatyrova, Eva-Maria Schmitz, Claudia Hube-Magg, Martina Kluth, Hartwig Huland, Markus Graefen, Chris Lawerenz, Gervaise H Henry, Takafumi N Yamaguchi, Alicia Malewska, Jan Meiners, Daniela Schilling, Eva Reisinger, Roland Eils, Matthias Schlesner, Douglas W Strand, Robert G Bristow, Paul C Boutros, Christof von Kalle, Dmitry Gordenin, Holger Sültmann, Benedikt Brors, Guido Sauter, Christoph Plass, Marie-Laure Yaspo, Jan O Korbel, Thorsten Schlomm, Joachim Weischenfeldt

    113 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    JournalCancer Cell
    Volume34
    Issue number6
    Pages (from-to)996-1011.e8
    ISSN1535-6108
    DOIs
    Publication statusPublished - 10 Dec 2018

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