The evolutionary history of lethal metastatic prostate cancer.
The evolutionary history of lethal metastatic prostate cancer.
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DOI：
10.1038/nature14347
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发表时间：
2015-04-16
期刊：
影响因子：
64.8
通讯作者：
Bova, G. Steven
中科院分区：
文献类型：
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作者：
Gundem, Gunes;Van Loo, Peter;Kremeyer, Barbara;Alexandrov, Ludmil B.;Tubio, Jose M. C.;Papaemmanuil, Elli;Brewer, Daniel S.;Kallio, Heini M. L.;Hoegnas, Gunilla;Annala, Matti;Kivinummi, Kati;Goody, Victoria;Latimer, Calli;O'Meara, Sarah;Dawson, Kevin J.;Isaacs, William;Emmert-Buck, Michael R.;Nykter, Matti;Foster, Christopher;Kote-Jarai, Zsofia;Easton, Douglas;Whitaker, Hayley C.;Neal, David E.;Cooper, Colin S.;Eeles, Rosalind A.;Visakorpi, Tapio;Campbell, Peter J.;McDermott, Ultan;Wedge, David C.;Bova, G. Steven
癌症是从一个持续的达尔文进化过程中出现的，通常会导致单个原发性肿瘤中的多个竞争性亚克隆。这一进化过程最终导致转移，这是90%癌症相关死亡的原因。然而，尽管它的临床重要性，很少有人知道的原则，管理癌细胞传播到远处的器官。虽然每个转移起源于单个肿瘤细胞的假设得到普遍支持，但最近使用小鼠癌症模型的研究表明存在多克隆播种和多个亚克隆之间的克隆间合作。在这项研究中，我们寻求人类恶性肿瘤中存在多克隆播种的确切证据，并在雄激素剥夺转移性前列腺癌的背景下建立不同转移灶之间的克隆关系。使用全基因组测序，我们在10名患者中描述了前列腺肿瘤的多发性转移。亚克隆结构的综合分析揭示了转移扩散的模式，在前所未有的细节。转移到转移扩散被认为是常见的，无论是通过从头单克隆种植的女儿转移，或在5例，通过转移部位之间的多个肿瘤克隆的转移。影响肿瘤抑制基因的病变通常作为单一事件发生，而参与雄激素受体信号传导的基因突变通常涉及不同转移的多个会聚事件。我们的研究结果详细阐明了转移扩散的复杂模式，并进一步加深了我们对前列腺癌雄激素剥夺治疗耐药性发展的理解。
Cancers emerge from an on-going Darwinian evolutionary process, often leading to multiple competing subclones within a single primary tumour. This evolutionary process culminates in the formation of metastases, which is the cause of 90% of cancer-related deaths. However, despite its clinical importance, little is known about the principles governing the dissemination of cancer cells to distant organs. Although the hypothesis that each metastasis originates from a single tumour cell is generally supported, recent studies using mouse models of cancer demonstrated the existence of polyclonal seeding from and inter-clonal cooperation between multiple subclones. In this study, we sought definitive evidence for the existence of polyclonal seeding in human malignancy and to establish the clonal relationship among different metastases in the context of androgen-deprived metastatic prostate cancer. Using whole genome sequencing, we characterised multiple metastases arising from prostate tumours in ten patients. Integrated analyses of subclonal architecture revealed the patterns of metastatic spread in unprecedented detail. Metastasis-to-metastasis spread was found to be common, either through de novo monoclonal seeding of daughter metastases or, in five cases, through the transfer of multiple tumour clones between metastatic sites. Lesions affecting tumour suppressor genes usually occur as single events, whereas mutations in genes involved in androgen receptor signalling commonly involve multiple, convergent events in different metastases. Our results elucidate in detail the complex patterns of metastatic spread and further our understanding of the development of resistance to androgen deprivation therapy in prostate cancer.
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影响因子：
64.5
作者：
McFadden DG;Papagiannakopoulos T;Taylor-Weiner A;Stewart C;Carter SL;Cibulskis K;Bhutkar A;McKenna A;Dooley A;Vernon A;Sougnez C;Malstrom S;Heimann M;Park J;Chen F;Farago AF;Dayton T;Shefler E;Gabriel S;Getz G;Jacks T
通讯作者：
Jacks T
影响因子：
50.3
作者：
Taylor BS;Schultz N;Hieronymus H;Gopalan A;Xiao Y;Carver BS;Arora VK;Kaushik P;Cerami E;Reva B;Antipin Y;Mitsiades N;Landers T;Dolgalev I;Major JE;Wilson M;Socci ND;Lash AE;Heguy A;Eastham JA;Scher HI;Reuter VE;Scardino PT;Sander C;Sawyers CL;Gerald WL
通讯作者：
Gerald WL
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
30.8
作者：
Zack, Travis I.;Schumacher, Steven E.;Carter, Scott L.;Cherniack, Andrew D.;Saksena, Gordon;Tabak, Barbara;Lawrence, Michael S.;Zhang, Cheng-Zhong;Wala, Jeremiah;Mermel, Craig H.;Sougnez, Carrie;Gabriel, Stacey B.;Hernandez, Bryan;Shen, Hui;Laird, Peter W.;Getz, Gad;Meyerson, Matthew;Beroukhim, Rameen
通讯作者：
Beroukhim, Rameen
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
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作者：
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