Publication Date:
2011-02-11
Description:
Prostate cancer is the second most common cause of male cancer deaths in the United States. However, the full range of prostate cancer genomic alterations is incompletely characterized. Here we present the complete sequence of seven primary human prostate cancers and their paired normal counterparts. Several tumours contained complex chains of balanced (that is, 'copy-neutral') rearrangements that occurred within or adjacent to known cancer genes. Rearrangement breakpoints were enriched near open chromatin, androgen receptor and ERG DNA binding sites in the setting of the ETS gene fusion TMPRSS2-ERG, but inversely correlated with these regions in tumours lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumours contained rearrangements that disrupted CADM2, and four harboured events disrupting either PTEN (unbalanced events), a prostate tumour suppressor, or MAGI2 (balanced events), a PTEN interacting protein not previously implicated in prostate tumorigenesis. Thus, genomic rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075885/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075885/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berger, Michael F -- Lawrence, Michael S -- Demichelis, Francesca -- Drier, Yotam -- Cibulskis, Kristian -- Sivachenko, Andrey Y -- Sboner, Andrea -- Esgueva, Raquel -- Pflueger, Dorothee -- Sougnez, Carrie -- Onofrio, Robert -- Carter, Scott L -- Park, Kyung -- Habegger, Lukas -- Ambrogio, Lauren -- Fennell, Timothy -- Parkin, Melissa -- Saksena, Gordon -- Voet, Douglas -- Ramos, Alex H -- Pugh, Trevor J -- Wilkinson, Jane -- Fisher, Sheila -- Winckler, Wendy -- Mahan, Scott -- Ardlie, Kristin -- Baldwin, Jennifer -- Simons, Jonathan W -- Kitabayashi, Naoki -- MacDonald, Theresa Y -- Kantoff, Philip W -- Chin, Lynda -- Gabriel, Stacey B -- Gerstein, Mark B -- Golub, Todd R -- Meyerson, Matthew -- Tewari, Ashutosh -- Lander, Eric S -- Getz, Gad -- Rubin, Mark A -- Garraway, Levi A -- 2 P50 CA090381-11/CA/NCI NIH HHS/ -- DP2 OD002750/OD/NIH HHS/ -- DP2 OD002750-01/OD/NIH HHS/ -- R33 CA126674/CA/NCI NIH HHS/ -- R33 CA126674-03/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Feb 10;470(7333):214-20. doi: 10.1038/nature09744.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21307934" target="_blank"〉PubMed〈/a〉
Keywords:
Carrier Proteins/genetics
;
Case-Control Studies
;
Cell Adhesion Molecules/genetics
;
Chromatin/genetics/metabolism
;
Chromosome Aberrations
;
Chromosome Breakpoints
;
Epigenesis, Genetic/genetics
;
Gene Expression Regulation, Neoplastic
;
Genome, Human/*genetics
;
Humans
;
Male
;
PTEN Phosphohydrolase/genetics/metabolism
;
Prostatic Neoplasms/*genetics
;
Recombination, Genetic/genetics
;
Signal Transduction/genetics
;
Transcription, Genetic
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
