Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer
dc.contributor.author | Tomlins, Scott A. | en_US |
dc.contributor.author | Laxman, Bharathi | en_US |
dc.contributor.author | Dhanasekaran, Saravana M. | en_US |
dc.contributor.author | Helgeson, Beth E. | en_US |
dc.contributor.author | Cao, Xuhong | en_US |
dc.contributor.author | Morris, David S. | en_US |
dc.contributor.author | Menon, Anjana | en_US |
dc.contributor.author | Jing, Xiaojun | en_US |
dc.contributor.author | Cao, Qi | en_US |
dc.contributor.author | Han, Bo | en_US |
dc.contributor.author | Yu, Jindan | en_US |
dc.contributor.author | Wang, Lei | en_US |
dc.contributor.author | Montie, James E. | en_US |
dc.contributor.author | Rubin, Mark A. | en_US |
dc.contributor.author | Pienta, Kenneth J. | en_US |
dc.contributor.author | Roulston, Diane | en_US |
dc.contributor.author | Shah, Rajal B. | en_US |
dc.contributor.author | Varambally, Sooryanarayana | en_US |
dc.contributor.author | Mehra, Rohit | en_US |
dc.contributor.author | Chinnaiyan, Arul M. | en_US |
dc.date.accessioned | 2009-06-01T17:29:36Z | |
dc.date.available | 2009-06-01T17:29:36Z | |
dc.date.issued | 2007-08-02 | en_US |
dc.identifier.citation | Tomlins, Scott A.; Laxman, Bharathi; Dhanasekaran, Saravana M.; Helgeson, Beth E.; Cao, Xuhong; Morris, David S.; Menon, Anjana; Jing, Xiaojun; Cao, Qi; Han, Bo; Yu, Jindan; Wang, Lei; Montie, James E.; Rubin, Mark A.; Pienta, Kenneth J.; Roulston, Diane; Shah, Rajal B.; Varambally, Sooryanarayana; Mehra, Rohit; Chinnaiyan, Arul M.. (2007) "Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer." Nature 448(7153): 595-U9. <http://hdl.handle.net/2027.42/62659> | en_US |
dc.identifier.issn | 0028-0836 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/62659 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17671502&dopt=citation | en_US |
dc.description.abstract | Recently, we identified recurrent gene fusions involving the 59 untranslated region of the androgen-regulated gene TMPRSS2 and the ETS (E26 transformation-specific) family genes ERG, ETV1 or ETV4 in most prostate cancers(1,2). Whereas TMPRSS2 ERG fusions are predominant, fewer TMPRSS2-ETV1 cases have been identified than expected on the basis of the frequency of high (outlier) expression of ETV1 (refs 3-13). Here we explore the mechanism of ETV1 outlier expression in human prostate tumours and prostate cancer cell lines. We identified previously unknown 59 fusion partners in prostate tumours with ETV1 outlier expression, including untranslated regions from a prostate-specific androgen-induced gene (SLC45A3) and an endogenous retroviral element (HERV-K_22q11.23), a prostate-specific androgen-repressed gene (C15orf21), and a strongly expressed housekeeping gene (HNRPA2B1). To study aberrant activation of ETV1, we identified two prostate cancer cell lines, LNCaP and MDA-PCa 2B, that had ETV1 outlier expression. Through distinct mechanisms, the entire ETV1 locus (7p21) is rearranged to a 1.5-megabase prostate-specific region at 14q13.3-14q21.1 in both LNCaP cells (cryptic insertion) and MDA- PCa 2B cells (balanced translocation). Because the common factor of these rearrangements is aberrant ETV1 overexpression, we recapitulated this event in vitro and in vivo, demonstrating that ETV1 overexpression in benign prostate cells and in the mouse prostate confers neoplastic phenotypes. Identification of distinct classes of ETS gene rearrangements demonstrates that dormant oncogenes can be activated in prostate cancer by juxtaposition to tissue-specific or ubiquitously active genomic loci. Subversion of active genomic regulatory elements may serve as a more generalized mechanism for carcinoma development. Furthermore, the identification of androgen-repressed and insensitive 59 fusion partners may have implications for the anti-androgen treatment of advanced prostate cancer. | en_US |
dc.format.extent | 635344 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Nature Publishing Group | en_US |
dc.source | Nature | en_US |
dc.title | Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Dept Pathol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationother | Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA | en_US |
dc.identifier.pmid | 17671502 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/62659/1/nature06024.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1038/nature06024 | en_US |
dc.identifier.source | Nature | en_US |
dc.contributor.authoremail | arul@umich.edu | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.