Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer
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 c...
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| Veröffentlicht in: | Cancer cell 2013-02, Vol.23 (2), p.159-170 |
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| creator | 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 |
| description | 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 |
| doi_str_mv | 10.1016/j.ccr.2013.01.002 |
| format | Article |
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► 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</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/j.ccr.2013.01.002</identifier><identifier>PMID: 23410972</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>Cancer cell, 2013-02, Vol.23 (2), p.159-170</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-f3a56707937b2ea25b7ed8e8e3d857406bf1aecc19e1afb1ce0fc127b09590e73</citedby><cites>FETCH-LOGICAL-c396t-f3a56707937b2ea25b7ed8e8e3d857406bf1aecc19e1afb1ce0fc127b09590e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1535610813000044$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23410972$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Weischenfeldt, Joachim</creatorcontrib><creatorcontrib>Simon, Ronald</creatorcontrib><creatorcontrib>Feuerbach, Lars</creatorcontrib><creatorcontrib>Schlangen, Karin</creatorcontrib><creatorcontrib>Weichenhan, Dieter</creatorcontrib><creatorcontrib>Minner, Sarah</creatorcontrib><creatorcontrib>Wuttig, Daniela</creatorcontrib><creatorcontrib>Warnatz, Hans-Jörg</creatorcontrib><creatorcontrib>Stehr, Henning</creatorcontrib><creatorcontrib>Rausch, Tobias</creatorcontrib><creatorcontrib>Jäger, Natalie</creatorcontrib><creatorcontrib>Gu, Lei</creatorcontrib><creatorcontrib>Bogatyrova, Olga</creatorcontrib><creatorcontrib>Stütz, Adrian M.</creatorcontrib><creatorcontrib>Claus, Rainer</creatorcontrib><creatorcontrib>Eils, Jürgen</creatorcontrib><creatorcontrib>Eils, Roland</creatorcontrib><creatorcontrib>Gerhäuser, Clarissa</creatorcontrib><creatorcontrib>Huang, Po-Hsien</creatorcontrib><creatorcontrib>Hutter, Barbara</creatorcontrib><creatorcontrib>Kabbe, Rolf</creatorcontrib><creatorcontrib>Lawerenz, Christian</creatorcontrib><creatorcontrib>Radomski, Sylwester</creatorcontrib><creatorcontrib>Bartholomae, Cynthia C.</creatorcontrib><creatorcontrib>Fälth, Maria</creatorcontrib><creatorcontrib>Gade, Stephan</creatorcontrib><creatorcontrib>Schmidt, Manfred</creatorcontrib><creatorcontrib>Amschler, Nina</creatorcontrib><creatorcontrib>Haß, Thomas</creatorcontrib><creatorcontrib>Galal, Rami</creatorcontrib><creatorcontrib>Gjoni, Jovisa</creatorcontrib><creatorcontrib>Kuner, Ruprecht</creatorcontrib><creatorcontrib>Baer, Constance</creatorcontrib><creatorcontrib>Masser, Sawinee</creatorcontrib><creatorcontrib>von Kalle, Christof</creatorcontrib><creatorcontrib>Zichner, Thomas</creatorcontrib><creatorcontrib>Benes, Vladimir</creatorcontrib><creatorcontrib>Raeder, Benjamin</creatorcontrib><creatorcontrib>Mader, Malte</creatorcontrib><creatorcontrib>Amstislavskiy, Vyacheslav</creatorcontrib><creatorcontrib>Avci, Meryem</creatorcontrib><creatorcontrib>Lehrach, Hans</creatorcontrib><creatorcontrib>Parkhomchuk, Dmitri</creatorcontrib><creatorcontrib>Sultan, Marc</creatorcontrib><creatorcontrib>Burkhardt, Lia</creatorcontrib><creatorcontrib>Graefen, Markus</creatorcontrib><creatorcontrib>Huland, Hartwig</creatorcontrib><creatorcontrib>Kluth, Martina</creatorcontrib><creatorcontrib>Krohn, Antje</creatorcontrib><creatorcontrib>Sirma, Hüseyin</creatorcontrib><creatorcontrib>Stumm, Laura</creatorcontrib><creatorcontrib>Steurer, Stefan</creatorcontrib><creatorcontrib>Grupp, Katharina</creatorcontrib><creatorcontrib>Sültmann, Holger</creatorcontrib><creatorcontrib>Sauter, Guido</creatorcontrib><creatorcontrib>Plass, Christoph</creatorcontrib><creatorcontrib>Brors, Benedikt</creatorcontrib><creatorcontrib>Yaspo, Marie-Laure</creatorcontrib><creatorcontrib>Korbel, Jan O.</creatorcontrib><creatorcontrib>Schlomm, Thorsten</creatorcontrib><title>Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer</title><title>Cancer cell</title><addtitle>Cancer Cell</addtitle><description>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</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Computational Biology</subject><subject>Gene Rearrangement</subject><subject>Genomics</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Receptors, Androgen - genetics</subject><subject>Serine Endopeptidases - genetics</subject><subject>Trans-Activators - genetics</subject><subject>Transcriptional Regulator 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Katharina</creatorcontrib><creatorcontrib>Sültmann, Holger</creatorcontrib><creatorcontrib>Sauter, Guido</creatorcontrib><creatorcontrib>Plass, Christoph</creatorcontrib><creatorcontrib>Brors, Benedikt</creatorcontrib><creatorcontrib>Yaspo, Marie-Laure</creatorcontrib><creatorcontrib>Korbel, Jan O.</creatorcontrib><creatorcontrib>Schlomm, Thorsten</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Weischenfeldt, Joachim</au><au>Simon, Ronald</au><au>Feuerbach, Lars</au><au>Schlangen, Karin</au><au>Weichenhan, Dieter</au><au>Minner, Sarah</au><au>Wuttig, Daniela</au><au>Warnatz, Hans-Jörg</au><au>Stehr, Henning</au><au>Rausch, Tobias</au><au>Jäger, Natalie</au><au>Gu, Lei</au><au>Bogatyrova, Olga</au><au>Stütz, Adrian M.</au><au>Claus, Rainer</au><au>Eils, Jürgen</au><au>Eils, Roland</au><au>Gerhäuser, Clarissa</au><au>Huang, Po-Hsien</au><au>Hutter, Barbara</au><au>Kabbe, Rolf</au><au>Lawerenz, Christian</au><au>Radomski, Sylwester</au><au>Bartholomae, Cynthia C.</au><au>Fälth, Maria</au><au>Gade, Stephan</au><au>Schmidt, Manfred</au><au>Amschler, Nina</au><au>Haß, Thomas</au><au>Galal, Rami</au><au>Gjoni, Jovisa</au><au>Kuner, Ruprecht</au><au>Baer, Constance</au><au>Masser, Sawinee</au><au>von Kalle, Christof</au><au>Zichner, Thomas</au><au>Benes, Vladimir</au><au>Raeder, Benjamin</au><au>Mader, Malte</au><au>Amstislavskiy, Vyacheslav</au><au>Avci, Meryem</au><au>Lehrach, Hans</au><au>Parkhomchuk, Dmitri</au><au>Sultan, Marc</au><au>Burkhardt, Lia</au><au>Graefen, Markus</au><au>Huland, Hartwig</au><au>Kluth, Martina</au><au>Krohn, Antje</au><au>Sirma, Hüseyin</au><au>Stumm, Laura</au><au>Steurer, Stefan</au><au>Grupp, Katharina</au><au>Sültmann, Holger</au><au>Sauter, Guido</au><au>Plass, Christoph</au><au>Brors, Benedikt</au><au>Yaspo, Marie-Laure</au><au>Korbel, Jan O.</au><au>Schlomm, Thorsten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer</atitle><jtitle>Cancer cell</jtitle><addtitle>Cancer Cell</addtitle><date>2013-02-11</date><risdate>2013</risdate><volume>23</volume><issue>2</issue><spage>159</spage><epage>170</epage><pages>159-170</pages><issn>1535-6108</issn><eissn>1878-3686</eissn><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.
► 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</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23410972</pmid><doi>10.1016/j.ccr.2013.01.002</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1535-6108 |
| ispartof | Cancer cell, 2013-02, Vol.23 (2), p.159-170 |
| issn | 1535-6108 1878-3686 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1288314842 |
| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 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 |
| title | Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T19%3A34%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Integrative%20Genomic%20Analyses%20Reveal%20an%20Androgen-Driven%20Somatic%20Alteration%20Landscape%20in%20Early-Onset%20Prostate%20Cancer&rft.jtitle=Cancer%20cell&rft.au=Weischenfeldt,%20Joachim&rft.date=2013-02-11&rft.volume=23&rft.issue=2&rft.spage=159&rft.epage=170&rft.pages=159-170&rft.issn=1535-6108&rft.eissn=1878-3686&rft_id=info:doi/10.1016/j.ccr.2013.01.002&rft_dat=%3Cproquest_cross%3E1288314842%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1288314842&rft_id=info:pmid/23410972&rft_els_id=S1535610813000044&rfr_iscdi=true |