Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories
- Gerhauser, C.
- Favero, F.
- Risch, T.
- Simon, R.
- Feuerbach, L.
- Assenov, Y.
- Heckmann, D.
- Sidiropoulos, N.
- Waszak, S.
- Hübschmann, D.
- Urbanucci, A.
- Girma, E.
- Kuryshev, V.
- Klimczak, L.
- Saini, N.
- Stütz, A.
- Weichenhan, D.
- Böttcher, L.
- Toth, R.
- Hendriksen, J.
- Koop, C.
- Lutsik, P.
- Matzk, S.
- Warnatz, H.
- Amstislavskiy, V.
- Feuerstein, C.
- Raeder, B.
- Bogatyrova, O.
- Schmitz, E.
- Hube-Magg, C.
- Kluth, M.
- Huland, H.
- Graefen, M.
- Lawerenz, C.
- Henry, G.
- Yamaguchi, T.
- Malewska, A.
- Meiners, J.
- Schilling, D.
- Reisinger, E.
- Eils, R.
- Schlesner, M.
- Strand, D.
- Bristow, R.
- Boutros, P.
- von Kalle, C.
- Gordenin, D.
- Sültmann, H.
- Brors, B.
- Sauter, G.
- Plass, C.
- Yaspo, M.
- Korbel, J.
- Schlomm, T.
- Weischenfeldt, J.
DOIAbstract
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 combin...
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