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

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  1. Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

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  3. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The landscape of genomic alterations across childhood cancers

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  3. SvABA: genome-wide detection of structural variants and indels by local assembly

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    Research output: Contribution to journalJournal articleResearchpeer-review

  • Joachim Weischenfeldt
  • Ronald Simon
  • Lars Feuerbach
  • Karin Schlangen
  • Dieter Weichenhan
  • Sarah Minner
  • Daniela Wuttig
  • Hans Jörg Warnatz
  • Henning Stehr
  • Tobias Rausch
  • Natalie Jäger
  • Lei Gu
  • Olga Bogatyrova
  • Adrian M. Stütz
  • Rainer Claus
  • Jürgen Eils
  • Roland Eils
  • Clarissa Gerhäuser
  • Po Hsien Huang
  • Barbara Hutter
  • Rolf Kabbe
  • Christian Lawerenz
  • Sylwester Radomski
  • Cynthia C. Bartholomae
  • Maria Fälth
  • Stephan Gade
  • Manfred Schmidt
  • Nina Amschler
  • Thomas Haß
  • Rami Galal
  • Jovisa Gjoni
  • Ruprecht Kuner
  • Constance Baer
  • Sawinee Masser
  • Christof von Kalle
  • Thomas Zichner
  • Vladimir Benes
  • Benjamin Raeder
  • Malte Mader
  • Vyacheslav Amstislavskiy
  • Meryem Avci
  • Hans Lehrach
  • Dmitri Parkhomchuk
  • Marc Sultan
  • Lia Burkhardt
  • Markus Graefen
  • Hartwig Huland
  • Martina Kluth
  • Antje Krohn
  • Hüseyin Sirma
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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.

Original languageEnglish
JournalCancer Cell
Volume23
Issue number2
Pages (from-to)159-170
Number of pages12
ISSN1535-6108
DOIs
Publication statusPublished - 11 Feb 2013
Externally publishedYes

ID: 55086586