title: Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer.
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.
authors: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstr. 1, 69117 Heidelberg, Germany.
authors: Joachim
authors: J
authors: Weischenfeldt
authors: Ronald
authors: R
authors: Simon
authors: Lars
authors: L
authors: Feuerbach
authors: Karin
authors: K
authors: Schlangen
authors: Dieter
authors: D
authors: Weichenhan
authors: Sarah
authors: S
authors: Minner
authors: Daniela
authors: D
authors: Wuttig
authors: Hans-Jörg
authors: HJ
authors: Warnatz
authors: Henning
authors: H
authors: Stehr
authors: Tobias
authors: T
authors: Rausch
authors: Natalie
authors: N
authors: Jäger
authors: Lei
authors: L
authors: Gu
authors: Olga
authors: O
authors: Bogatyrova
authors: Adrian M
authors: AM
authors: Stütz
authors: Rainer
authors: R
authors: Claus
authors: Jürgen
authors: J
authors: Eils
authors: Roland
authors: R
authors: Eils
authors: Clarissa
authors: C
authors: Gerhäuser
authors: Po-Hsien
authors: PH
authors: Huang
authors: Barbara
authors: B
authors: Hutter
authors: Rolf
authors: R
authors: Kabbe
authors: Christian
authors: C
authors: Lawerenz
authors: Sylwester
authors: S
authors: Radomski
authors: Cynthia C
authors: CC
authors: Bartholomae
authors: Maria
authors: M
authors: Fälth
authors: Stephan
authors: S
authors: Gade
authors: Manfred
authors: M
authors: Schmidt
authors: Nina
authors: N
authors: Amschler
authors: Thomas
authors: T
authors: Haß
authors: Rami
authors: R
authors: Galal
authors: Jovisa
authors: J
authors: Gjoni
authors: Ruprecht
authors: R
authors: Kuner
authors: Constance
authors: C
authors: Baer
authors: Sawinee
authors: S
authors: Masser
authors: Christof
authors: C
authors: von Kalle
authors: Thomas
authors: T
authors: Zichner
authors: Vladimir
authors: V
authors: Benes
authors: Benjamin
authors: B
authors: Raeder
authors: Malte
authors: M
authors: Mader
authors: Vyacheslav
authors: V
authors: Amstislavskiy
authors: Meryem
authors: M
authors: Avci
authors: Hans
authors: H
authors: Lehrach
authors: Dmitri
authors: D
authors: Parkhomchuk
authors: Marc
authors: M
authors: Sultan
authors: Lia
authors: L
authors: Burkhardt
authors: Markus
authors: M
authors: Graefen
authors: Hartwig
authors: H
authors: Huland
authors: Martina
authors: M
authors: Kluth
authors: Antje
authors: A
authors: Krohn
authors: Hüseyin
authors: H
authors: Sirma
authors: Laura
authors: L
authors: Stumm
authors: Stefan
authors: S
authors: Steurer
authors: Katharina
authors: K
authors: Grupp
authors: Holger
authors: H
authors: Sültmann
authors: Guido
authors: G
authors: Sauter
authors: Christoph
authors: C
authors: Plass
authors: Benedikt
authors: B
authors: Brors
authors: Marie-Laure
authors: ML
authors: Yaspo
authors: Jan O
authors: JO
authors: Korbel
authors: Thorsten
authors: T
authors: Schlomm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019295:Computational Biology; D015321:Gene Rearrangement; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: C410798:AR protein, human; C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; D011944:Receptors, Androgen; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human