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

Weischenfeldt, J., Simon, R., Feuerbach, L., Schlangen, K., Weichenhan, D., Minner, S., et al. (2013). Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell, 23(2), 159-70. doi:S1535-6108(13)00004-4 [pii]10.1016/j.ccr.2013.01.002.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0018-F403-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0018-F405-C
Genre: Journal Article

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2013
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© 2013 Elsevier Inc. All rights reserved.
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 Creators:
Weischenfeldt, J., Author
Simon, R., Author
Feuerbach, L., Author
Schlangen, K.1, Author
Weichenhan, D., Author
Minner, S., Author
Wuttig, D., Author
Warnatz, H. J.1, Author              
Stehr, H.2, Author              
Rausch, T., Author
Jager, N., Author
Gu, L., Author
Bogatyrova, O., Author
Stutz, A. M., Author
Claus, R., Author
Eils, J., Author
Eils, R., Author
Gerhauser, C., Author
Huang, P. H., Author
Hutter, B., Author
Kabbe, R., AuthorLawerenz, C., AuthorRadomski, S., AuthorBartholomae, C. C., AuthorFalth, M., AuthorGade, S., AuthorSchmidt, M., AuthorAmschler, N., AuthorHass, T., AuthorGalal, R., AuthorGjoni, J., AuthorKuner, R., AuthorBaer, C., AuthorMasser, S., Authorvon Kalle, C., AuthorZichner, T., AuthorBenes, V., AuthorRaeder, B., AuthorMader, M., AuthorAmstislavskiy, V.3, Author              Avci, M., AuthorLehrach, H.4, Author              Parkhomchuk, D.4, Author              Sultan, M.3, Author              Burkhardt, L., AuthorGraefen, M., AuthorHuland, H., AuthorKluth, M., AuthorKrohn, A., AuthorSirma, H., AuthorStumm, L., AuthorSteurer, S., AuthorGrupp, K., AuthorSultmann, H., AuthorSauter, G., AuthorPlass, C., AuthorBrors, B., AuthorYaspo Lehrach, Marie L.3, Author              Korbel, J. O., AuthorSchlomm, T., Author more..
Affiliations:
1Department of Biomedical Optics, Max Planck Institute for Medical Research, Max Planck Society, ou_1497699              
2Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433554              
3Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479652              
4Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: 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
 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.

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Language(s): eng - English
 Dates: 2013-02-162013
 Publication Status: Published in print
 Pages: -
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Title: Cancer Cell
  Other : Cancer Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 23 (2) Sequence Number: - Start / End Page: 159 - 70 Identifier: ISSN: 1535-6108
CoNE: https://pure.mpg.de/cone/journals/resource/111025129473004