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

Publication date: 10 December 2018Source: Cancer Cell, Volume 34, Issue 6Author(s): 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. HendriksenSummaryIdentifying 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.Graphical Abstract
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research