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Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer
Ist Teil von
Cancer cell, 2013-02, Vol.23 (2), p.159-170
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2013
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ）
Beschreibungen/Notizen
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.
► Genome sequencing revealed age-related genetic alterations in PCA ► Early-onset PCAs display a specific abundance of androgen-driven rearrangements ► These age-linked alterations coincide with activity levels of the androgen receptor ► This is an observation of age-specific DNA alterations in a common cancer