Abstract
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.
Original language | English |
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Pages (from-to) | 214-220 |
Number of pages | 7 |
Journal | Nature |
Volume | 470 |
Issue number | 7333 |
DOIs | |
State | Published - 10 Feb 2011 |
Externally published | Yes |
Bibliographical note
Funding Information:Acknowledgements We thank R. Leung and all members of the Broad Institute Sequencing Platform. This work was supported by the Prostate Cancer Foundation/ Movember (T.R.G., M.A.R., L.A.G.), the Howard Hughes Medical Institute (T.R.G.), the National Human Genome Research Institute (S.B.G., E.S.L.), the Kohlberg Foundation (P.W.K., L.A.G.), the National Cancer Institute (NCI; F.D., M.A.R., M.M.), the NCI Early Detection Research Network (M.A.R.), the National Institutes of Health (L.A.G.), the Department of Defense (F.D.), the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE grant 2 P50 CA090381-11 (P.W.K.), and the Starr Cancer Consortium (M.F.B., F.D., M.A.R., L.A.G.).