@article{58bda6edd1d0417ca2fd71f201fa8e84,
title = "The genomic complexity of primary human prostate cancer",
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-{\texttrademark}) 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.",
author = "Berger, {Michael F.} and Lawrence, {Michael S.} and Francesca Demichelis and Yotam Drier and Kristian Cibulskis and Sivachenko, {Andrey Y.} and Andrea Sboner and Raquel Esgueva and Dorothee Pflueger and Carrie Sougnez and Robert Onofrio and Carter, {Scott L.} and Kyung Park and Lukas Habegger and Lauren Ambrogio and Timothy Fennell and Melissa Parkin and Gordon Saksena and Douglas Voet and Ramos, {Alex H.} and Pugh, {Trevor J.} and Jane Wilkinson and Sheila Fisher and Wendy Winckler and Scott Mahan and Kristin Ardlie and Jennifer Baldwin and Simons, {Jonathan W.} and Naoki Kitabayashi and MacDonald, {Theresa Y.} and Kantoff, {Philip W.} and Lynda Chin and Gabriel, {Stacey B.} and Gerstein, {Mark B.} and Golub, {Todd R.} and Matthew Meyerson and Ashutosh Tewari and Lander, {Eric S.} and Gad Getz and Rubin, {Mark A.} and Garraway, {Levi A.}",
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.).",
year = "2011",
month = feb,
day = "10",
doi = "10.1038/nature09744",
language = "الإنجليزيّة",
volume = "470",
pages = "214--220",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",
number = "7333",
}
