Organoid cultures derived from patients with advanced prostate cancer.
Organoid cultures derived from patients with advanced prostate cancer.
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DOI：
10.1016/j.cell.2014.08.016
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发表时间：
2014-09-25
期刊：
影响因子：
64.5
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Gao D;Vela I;Sboner A;Iaquinta PJ;Karthaus WR;Gopalan A;Dowling C;Wanjala JN;Undvall EA;Arora VK;Wongvipat J;Kossai M;Ramazanoglu S;Barboza LP;Di W;Cao Z;Zhang QF;Sirota I;Ran L;MacDonald TY;Beltran H;Mosquera JM;Touijer KA;Scardino PT;Laudone VP;Curtis KR;Rathkopf DE;Morris MJ;Danila DC;Slovin SF;Solomon SB;Eastham JA;Chi P;Carver B;Rubin MA;Scher HI;Clevers H;Sawyers CL;Chen Y
由于缺乏能够概括人类前列腺癌多样性的体外前列腺癌模型，阻碍了了解疾病发病机制和治疗反应的进展。使用3D“类器官”系统，我们报告了从活检标本和循环肿瘤细胞中长期培养前列腺癌的成功。前七个完全表征的类器官系概括了前列腺癌亚型的分子多样性，包括TMPRSS 2-ERG融合、SPOP突变、SPINK 1过表达和CHD 1缺失。全外显子组测序显示突变负荷低，与基因组学研究一致，但FOXA 1和PIK 3R 1突变，以及晚期疾病中报道的DNA修复和染色质修饰剂途径突变。p53和RB肿瘤抑制途径功能的丧失是跨类器官系共享的最常见特征。这里描述的方法应该能够产生大量的患者来源的前列腺癌细胞系，适合遗传和药理学研究。
The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D “organoid” system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression and CHD1 loss. Whole exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1, as well as of DNA repair and chromatin modifier pathways that have been reported in advanced disease. Loss of p53 and RB tumor suppressor pathway function are the most common feature shared across the organoid lines. The methodology described here should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
8
作者：
Liu, W.;Lindberg, J.;Sui, G.;Luo, J.;Egevad, L.;Li, T.;Xie, C.;Wan, M.;Kim, S-T;Wang, Z.;Turner, A. R.;Zhang, Z.;Feng, J.;Yan, Y.;Sun, J.;Bova, G. S.;Ewing, C. M.;Yan, G.;Gielzak, M.;Cramer, S. D.;Vessella, R. L.;Zheng, S. L.;Gronberg, H.;Isaacs, W. B.;Xu, J.
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Xu, J.
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Balbas MD;Evans MJ;Hosfield DJ;Wongvipat J;Arora VK;Watson PA;Chen Y;Greene GL;Shen Y;Sawyers CL
通讯作者：
Sawyers CL
影响因子：
64.8
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Garnett, Mathew J.;Edelman, Elena J.;Heidorn, Sonja J.;Greenman, Chris D.;Dastur, Anahita;Lau, King Wai;Greninger, Patricia;Thompson, I. Richard;Luo, Xi;Soares, Jorge;Liu, Qingsong;Iorio, Francesco;Surdez, Didier;Chen, Li;Milano, Randy J.;Bignell, Graham R.;Tam, Ah T.;Davies, Helen;Stevenson, Jesse A.;Barthorpe, Syd;Lutz, Stephen R.;Kogera, Fiona;Lawrence, Karl;McLaren-Douglas, Anne;Mitropoulos, Xeni;Mironenko, Tatiana;Thi, Helen;Richardson, Laura;Zhou, Wenjun;Jewitt, Frances;Zhang, Tinghu;O'Brien, Patrick;Boisvert, Jessica L.;Price, Stacey;Hur, Wooyoung;Yang, Wanjuan;Deng, Xianming;Butler, Adam;Choi, Hwan Geun;Chang, JaeWon;Baselga, Jose;Stamenkovic, Ivan;Engelman, Jeffrey A.;Sharma, Sreenath V.;Delattre, Olivier;Saez-Rodriguez, Julio;Gray, Nathanael S.;Settleman, Jeffrey;Futreal, P. Andrew;Haber, Daniel A.;Stratton, Michael R.;Ramaswamy, Sridhar;McDermott, Ultan;Benes, Cyril H.
通讯作者：
Benes, Cyril H.
影响因子：
64.5
作者：
Arora VK;Schenkein E;Murali R;Subudhi SK;Wongvipat J;Balbas MD;Shah N;Cai L;Efstathiou E;Logothetis C;Zheng D;Sawyers CL
通讯作者：
Sawyers CL