1. Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories.
- Author
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Gerhauser, Clarissa, Favero, Francesco, Risch, Thomas, Simon, Ronald, Feuerbach, Lars, Assenov, Yassen, Heckmann, Doreen, Sidiropoulos, Nikos, Waszak, Sebastian M, Hübschmann, Daniel, Urbanucci, Alfonso, Girma, Etsehiwot G, Kuryshev, Vladimir, Klimczak, Leszek J, Saini, Natalie, Stütz, Adrian M, Weichenhan, Dieter, Böttcher, Lisa-Marie, Toth, Reka, Hendriksen, Josephine D, Koop, Christina, Lutsik, Pavlo, Matzk, Sören, Warnatz, Hans-Jörg, Amstislavskiy, Vyacheslav, Feuerstein, Clarissa, Raeder, Benjamin, Bogatyrova, Olga, Schmitz, Eva-Maria, Hube-Magg, Claudia, Kluth, Martina, Huland, Hartwig, Graefen, Markus, Lawerenz, Chris, Henry, Gervaise H, Yamaguchi, Takafumi N, Malewska, Alicia, Meiners, Jan, Schilling, Daniela, Reisinger, Eva, Eils, Roland, Schlesner, Matthias, Strand, Douglas W, Bristow, Robert G, Boutros, Paul C, von Kalle, Christof, Gordenin, Dmitry, Sültmann, Holger, Brors, Benedikt, Sauter, Guido, Plass, Christoph, Yaspo, Marie-Laure, Korbel, Jan O, Schlomm, Thorsten, and Weischenfeldt, Joachim
- Subjects
Humans ,Prostatic Neoplasms ,RNA-Binding Proteins ,Risk Factors ,Evolution ,Molecular ,DNA Methylation ,Gene Expression Regulation ,Neoplastic ,Mutation ,Adult ,Middle Aged ,Male ,Transcriptome ,Biomarkers ,Tumor ,Whole Genome Sequencing ,APOBEC ,cancer genomics ,early-onset cancer ,epigenetic risk-score ,mutational processes ,prostate cancer ,structural variants ,tumor evolution ,tumor evolution prediction ,Human Genome ,Aging ,Prevention ,Cancer ,Urologic Diseases ,Prostate Cancer ,Genetics ,4.1 Discovery and preclinical testing of markers and technologies ,Aetiology ,2.1 Biological and endogenous factors ,Detection ,screening and diagnosis ,Neurosciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - 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.
- Published
- 2018