Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer

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• 作者：Joachim Weischenfeldt¹ ; ¹⁴ ; Ronald Simon² ; ¹⁴ ; Lars Feuerbach⁴ ; ¹⁴ ; Karin Schlangen⁸ ; ¹⁴ ; Dieter Weichenhan⁵ ; ¹⁴ ; Sarah Minner² ; ¹⁴ ; Daniela Wuttig⁶ ; ¹⁴ ; Hans-Jö ; rg Warnatz⁸ ; Henning Stehr⁸ ; Tobias Rausch¹ ; Natalie Jä ; ger⁴ ; Lei Gu⁵ ; Olga Bogatyrova⁵ ; Adrian M. Stü ; tz¹ ; Rainer Claus⁵ ; Jü ; rgen Eils⁴ ; Roland Eils⁴ ; ¹² ; Clarissa Gerhä ; user⁵ ; Po-Hsien Huang⁵ ; Barbara Hutter⁴ ; Rolf Kabbe⁴ ; Christian Lawerenz⁴ ; Sylwester Radomski⁴ ; Cynthia C. Bartholomae⁷ ; Maria Fä ; lth⁶ ; Stephan Gade⁶ ; Manfred Schmidt⁷ ; Nina Amschler² ; Thomas Haß ; ² ; Rami Galal² ; Jovisa Gjoni² ; Ruprecht Kuner⁶ ; Constance Baer⁵ ; Sawinee Masser² ; Christof von Kalle⁷ ; Thomas Zichner¹ ; Vladimir Benes¹³ ; Benjamin Raeder¹ ; Malte Mader⁹ ; Vyacheslav Amstislavskiy⁸ ; Meryem Avci⁷ ; Hans Lehrach⁸ ; Dmitri Parkhomchuk⁸ ; Marc Sultan⁸ ; Lia Burkhardt² ; Markus Graefen³ ; Hartwig Huland³ ; Martina Kluth² ; Antje Krohn² ; Hü ; seyin Sirma² ; Laura Stumm² ; Stefan Steurer² ; Katharina Grupp² ; Holger Sü ; ltmann⁶ ; ¹⁵ ; Guido Sauter² ; ¹⁵ ; Christoph Plass⁵ ; ¹⁵ ; Benedikt Brors⁴ ; ¹⁵ ; Marie-Laure Yaspo⁸ ; ¹⁵ ; Jan O. Korbel¹ ; ¹⁰ ; ¹⁵ ; ^{jan.korbel@embl.de} ; Thorsten Schlomm³ ; ¹¹ ; ¹⁵
• 刊名：Cancer Cell
• 出版年：2013
• 出版时间：11 February, 2013
• 年：2013
• 卷：23
• 期：2
• 页码：159-170
• 全文大小：1230 K

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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.