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

Weischenfeldt, Joachim ; Simon, Ronald ; Feuerbach, Lars ; Schlangen, Karin ; Weichenhan, Dieter ; Minner, Sarah ; Wuttig, Daniela ; Warnatz, Hans-Jörg ; Stehr, Henning ; Rausch, Tobias ; Jäger, Natalie ; Gu, Lei ; Bogatyrova, Olga ; Stütz, Adrian M. ; Claus, Rainer ; Eils, Jürgen ; Eils, Roland ; Gerhäuser, Clarissa ; Huang, Po-Hsien ; Hutter, Barbara ; Kabbe, Rolf ; Lawerenz, Christian ; Radomski, Sylwester ; Bartholomae, Cynthia C. ; Fälth, Maria ; Gade, Stephan ; Schmidt, Manfred ; Amschler, Nina ; Haß, Thomas ; Galal, Rami ; Gjoni, Jovisa ; Kuner, Ruprecht ; Baer, Constance ; Masser, Sawinee ; von Kalle, Christof ; Zichner, Thomas ; Benes, Vladimir ; Raeder, Benjamin ; Mader, Malte ; Amstislavskiy, Vyacheslav ; Avci, Meryem ; Lehrach, Hans ; Parkhomchuk, Dmitri ; Sultan, Marc ; Burkhardt, Lia ; Graefen, Markus ; Huland, Hartwig ; Kluth, Martina ; Krohn, Antje ; Sirma, Hüseyin ; Stumm, Laura ; Steurer, Stefan ; Grupp, Katharina ; Sültmann, Holger ; Sauter, Guido ; Plass, Christoph ; Brors, Benedikt ; Yaspo, Marie-Laure ; Korbel, Jan O. ; Schlomm, Thorsten

Cancer cell, 2013-02, Vol.23 (2), p.159-170 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer
Autor: Weischenfeldt, Joachim ; Simon, Ronald ; Feuerbach, Lars ; Schlangen, Karin ; Weichenhan, Dieter ; Minner, Sarah ; Wuttig, Daniela ; Warnatz, Hans-Jörg ; Stehr, Henning ; Rausch, Tobias ; Jäger, Natalie ; Gu, Lei ; Bogatyrova, Olga ; Stütz, Adrian M. ; Claus, Rainer ; Eils, Jürgen ; Eils, Roland ; Gerhäuser, Clarissa ; Huang, Po-Hsien ; Hutter, Barbara ; Kabbe, Rolf ; Lawerenz, Christian ; Radomski, Sylwester ; Bartholomae, Cynthia C. ; Fälth, Maria ; Gade, Stephan ; Schmidt, Manfred ; Amschler, Nina ; Haß, Thomas ; Galal, Rami ; Gjoni, Jovisa ; Kuner, Ruprecht ; Baer, Constance ; Masser, Sawinee ; von Kalle, Christof ; Zichner, Thomas ; Benes, Vladimir ; Raeder, Benjamin ; Mader, Malte ; Amstislavskiy, Vyacheslav ; Avci, Meryem ; Lehrach, Hans ; Parkhomchuk, Dmitri ; Sultan, Marc ; Burkhardt, Lia ; Graefen, Markus ; Huland, Hartwig ; Kluth, Martina ; Krohn, Antje ; Sirma, Hüseyin ; Stumm, Laura ; Steurer, Stefan ; Grupp, Katharina ; Sültmann, Holger ; Sauter, Guido ; Plass, Christoph ; Brors, Benedikt ; Yaspo, Marie-Laure ; Korbel, Jan O. ; Schlomm, Thorsten
Assuntos: Adult ; Aged ; Aged, 80 and over ; Computational Biology ; Gene Rearrangement ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Oncogene Proteins, Fusion - genetics ; Prostatic Neoplasms - genetics ; Receptors, Androgen - genetics ; Serine Endopeptidases - genetics ; Trans-Activators - genetics ; Transcriptional Regulator ERG
É parte de: Cancer cell, 2013-02, Vol.23 (2), p.159-170
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: 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
Editor: United States: Elsevier Inc
Idioma: Inglês

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

United States: Elsevier Inc

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