期刊
CANCER CELL
卷 23, 期 2, 页码 159-170出版社
CELL PRESS
DOI: 10.1016/j.ccr.2013.01.002
关键词
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资金
- German Federal Ministry of Education and Science in the program for medical genome research (FKZ) [01KU1001A, 01KU1001B, 01KU1001C, 01KU1001D]
- Alexander von Humboldt Foundation
- European Commission [Health-F2-2010-260791]
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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