ICGC Project on Early Onset Prostate Cancer
Prostate cancer is the most frequent malignant tumor in males and the second most frequent cause of cancer-related death. Currently, in Germany, more than 60,000 prostate cancers are diagnosed every year. Although most of these patients are treated in a curative attempt, more than 10,000 German men die from prostate cancer annually. Owing to the demographic changes of our society, a further doubling of prostate cancer incidences during the next 20 years is expected.
Figure 1. Integrative molecular analysis of early onset prostate cancer (EOPCA)
© Cancer Cell
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 (Figure 1). 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 (Gerhauser et al., Cancer Cell 2018).
Ongoing projects:
- Comprehensive characterization of the prostate cancer DNA methylome by whole-genome bisulfite sequencing (Batra et al., in preparation)
- Prostate cancer heterogeneity deconvolution through single cell profiling of chromatin accessibility and transcriptomic output (in collaboration with Mathieu Lupien as a Joint Tandem Research Project within the DKFZ-Princess Margaret Cancer Center Clinician and Medical Scientist Program, Furlano et al., in preparation)
- The epigenome landscape of prostate cancer (collaborative project in the Pan-Prostate Cancer Group (PPCG).
© made with BioRender
Publications:
- Weischenfeldt et al., Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell (2013)
- Brocks et al., Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer. Cell Reports (2014)
- Gerhauser et al., Molecular evolution of early onset prostate cancer identifies molecular risk markers and clinical trajectories. Cancer Cell (2018)
- Toth et al., Random forest-based modelling to detect biomarkers for prostate cancer progression (Clinical Epigenetics 2019)
- PCAWG, Pan-cancer analysis of whole genomes (Nature 2020)