[PDF][PDF] Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer

J Weischenfeldt, R Simon, L Feuerbach, K Schlangen… - Cancer cell, 2013 - cell.com
J Weischenfeldt, R Simon, L Feuerbach, K Schlangen, D Weichenhan, S Minner, D Wuttig…
Cancer cell, 2013cell.com
Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of
prostate cancer. 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 …
Summary
Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. 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.
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