The genomic complexity of primary human prostate cancer.
The genomic complexity of primary human prostate cancer.
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DOI：
10.1038/nature09744
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发表时间：
2011-02-10
期刊：
影响因子：
64.8
通讯作者：
Garraway, Levi A.
中科院分区：
文献类型：
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作者：
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.
前列腺癌是美国男性癌症死亡的第二大原因。在这里，我们介绍了七个主要前列腺癌及其配对的正常对应物的完整序列。几个肿瘤包含复杂的链条的平衡重排，发生在已知的癌症基因内或附近。在ETS基因融合TMPRSS2-ERG的环境中，将重排的断点富集在开放的染色质，雄激素受体和ERG DNA结合位点，但与缺乏ETS融合的肿瘤中的这些区域成反比。该观察结果表明染色质或转录调节与基因组畸变的起源之间存在联系。三个肿瘤包含破坏CADM2的重排，四个爆炸事件破坏了PTEN（不平衡事件），前列腺肿瘤抑制剂或MAGI2（平衡事件）（平衡事件），PTEN相互作用的蛋白质以前不涉及前列腺肿瘤。因此，基因组重排可能是由转录或染色质畸变引起的，以参与前列腺肿瘤的机制。
Prostate cancer is the second most common cause of male cancer deaths in the United States. Here we present the complete sequence of seven primary prostate cancers and their paired normal counterparts. Several tumors contained complex chains of balanced 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 tumors lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumors contained rearrangements that disrupted CADM2, and four harbored events disrupting either PTEN (unbalanced events), a prostate tumor 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 to engage prostate tumorigenic mechanisms.
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影响因子：
30.8
作者：
Carver, Brett S.;Tran, Jennifer;Gopalan, Anuradha;Chen, Zhenbang;Shaikh, Safa;Carracedo, Arkaitz;Alimonti, Andrea;Nardella, Caterina;Varmeh, Shohreh;Scardino, Peter T.;Cordon-Cardo, Carlos;Gerald, William;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo
影响因子：
64.8
作者：
通讯作者：
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
30.8
作者：
通讯作者：
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影响因子：
64.8
作者：
通讯作者：
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