ICGC Project on Early Onset Prostate Cancer

Large-scale tissue microarray analyses depict age relationships of the androgen-driven ETS-fusion protein TMPRSS2:ERG in early onset (EO)-PCA, and of nonandrogen-associated rearrangements in elderly-onset PCA. Frequency of assessed protein (rings) and binomial logistic regressions (lines) depict ERG overexpression (blue), TMPRSS2:ERG fusion gene presence (orange), chromosome 6q deletion (purple), and PTEN deletion/disruption (green) as a function of patient age (from Weischenfeldt et al., Cancer Cell 2013).
© Cancer Cell

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.

In cooperation with partners from the University Medical Center Hamburg-Eppendorf (UKE), Max Planck Institute for Molecular Genetics (MPI-MG), European Molecular Biology Laboratory (EMBL), National Center for Tumor Diseases Heidelberg (NCT) and several groups from the German Cancer Researhc Center (DKFZ) we will analyze the genome and epigenome of early onset prostate cancer (i.e. diagnosis below the age of 50).

To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA (Weischenfeldt et al., 2013)

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