Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer.

  • Joachim Weischenfeldt (Geteilte/r Erstautor/in)
  • Ronald Simon (Geteilte/r Erstautor/in)
  • Lars Feuerbach (Geteilte/r Erstautor/in)
  • Karin Schlangen (Geteilte/r Erstautor/in)
  • Dieter Weichenhan (Geteilte/r Erstautor/in)
  • Sarah Minner (Geteilte/r Erstautor/in)
  • Daniela Wuttig (Geteilte/r Erstautor/in)
  • 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
  • Laura Stumm
  • Stefan Steurer
  • Katharina Grupp
  • Holger Sültmann (Geteilte/r Letztautor/in)
  • Guido Sauter (Geteilte/r Letztautor/in)
  • Christoph Plass (Geteilte/r Letztautor/in)
  • Benedikt Brors (Geteilte/r Letztautor/in)
  • Marie-Laure Yaspo (Geteilte/r Letztautor/in)
  • Jan O Korbel (Geteilte/r Letztautor/in)
  • Thorsten Schlomm (Geteilte/r Letztautor/in)

Abstract

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.

Bibliografische Daten

OriginalspracheEnglisch
Aufsatznummer2
ISSN1535-6108
DOIs
StatusVeröffentlicht - 2013
pubmed 23410972