Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing.
Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing.
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DOI：
10.1016/j.cell.2014.02.031
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发表时间：
2014-03-13
期刊：
影响因子：
64.5
通讯作者：
Jacks T
中科院分区：
文献类型：
--
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
小细胞肺癌（SCLC）是一种高致死率、与吸烟相关的癌症，很少有已知的可靶向基因改变。通过基因组测序，我们描述了由Trp53和Rb1缺失引发的SCLC基因工程小鼠模型（GEMM）的体细胞进化。我们发现了DNA拷贝数的改变和复杂的基因组重排，并证明了在没有烟草诱变剂的情况下，体细胞点突变频率较低。针对肿瘤抑制因子Pten的改变发生在研究的大多数小鼠SCLC中，工程化的Pten缺失加速了小鼠SCLC，并消除了Trp53中Chr19的缺失；Rb1;Pten复合突变肿瘤。最后，通过对相关原发肿瘤和转移性肿瘤家族的比较测序，我们发现了小鼠SCLC多克隆和顺序转移扩散的证据。我们提出了一个SCLC肿瘤发生的时间模型，该模型对人类SCLC治疗和GEMMs中癌症基因组进化的性质具有重要意义。
Small cell lung carcinoma (SCLC) is a highly lethal, smoking-associated cancer with few known targetable genetic alterations. Using genome sequencing, we characterized the somatic evolution of a genetically engineered mouse model (GEMM) of SCLC initiated by loss of Trp53 and Rb1. We identified alterations in DNA copy number and complex genomic rearrangements and demonstrated a low somatic point mutation frequency in the absence of tobacco mutagens. Alterations targeting the tumor suppressor Pten occurred in the majority of murine SCLC studied, and engineered Pten deletion accelerated murine SCLC and abrogated loss of Chr19 in Trp53; Rb1; Pten compound mutant tumors. Finally, we found evidence for polyclonal and sequential metastatic spread of murine SCLC by comparative sequencing of families of related primary tumors and metastases. We propose a temporal model of SCLC tumorigenesis with implications for human SCLC therapeutics and the nature of cancer-genome evolution in GEMMs.
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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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DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
DOI：
10.1073/pnas.1108237108
发表时间：
2011-09-13
影响因子：
11.1
作者：
Ilic, Nina;Utermark, Tamara;Roberts, Thomas M.
通讯作者：
Roberts, Thomas M.
影响因子：
64.8
作者：
Biankin, Andrew V.;Waddell, Nicola;Kassahn, Karin S.;Gingras, Marie-Claude;Muthuswamy, Lakshmi B.;Johns, Amber L.;Miller, David K.;Wilson, Peter J.;Patch, Ann-Marie;Wu, Jianmin;Chang, David K.;Cowley, Mark J.;Gardiner, Brooke B.;Song, Sarah;Harliwong, Ivon;Idrisoglu, Senel;Nourse, Craig;Nourbakhsh, Ehsan;Manning, Suzanne;Wani, Shivangi;Gongora, Milena;Pajic, Marina;Scarlett, Christopher J.;Gill, Anthony J.;Pinho, Andreia V.;Rooman, Ilse;Anderson, Matthew;Holmes, Oliver;Leonard, Conrad;Taylor, Darrin;Wood, Scott;Xu, Qinying;Nones, Katia;Fink, J. Lynn;Christ, Angelika;Bruxner, Tim;Cloonan, Nicole;Kolle, Gabriel;Newell, Felicity;Pinese, Mark;Mead, R. Scott;Humphris, Jeremy L.;Kaplan, Warren;Jones, Marc D.;Colvin, Emily K.;Nagrial, Adnan M.;Humphrey, Emily S.;Chou, Angela;Chin, Venessa T.;Chantrill, Lorraine A.;Mawson, Amanda;Samra, Jaswinder S.;Kench, James G.;Lovell, Jessica A.;Daly, Roger J.;Merrett, Neil D.;Toon, Christopher;Epari, Krishna;Nguyen, Nam Q.;Barbour, Andrew;Zeps, Nikolajs;Kakkar, Nipun;Zhao, Fengmei;Wu, Yuan Qing;Wang, Min;Muzny, Donna M.;Fisher, William E.;Brunicardi, F. Charles;Hodges, Sally E.;Reid, Jeffrey G.;Drummond, Jennifer;Chang, Kyle;Han, Yi;Lewis, Lora R.;Dinh, Huyen;Buhay, Christian J.;Beck, Timothy;Timms, Lee;Sam, Michelle;Begley, Kimberly;Brown, Andrew;Pai, Deepa;Panchal, Ami;Buchner, Nicholas;De Borja, Richard;Denroche, Robert E.;Yung, Christina K.;Serra, Stefano;Onetto, Nicole;Mukhopadhyay, Debabrata;Tsao, Ming-Sound;Shaw, Patricia A.;Petersen, Gloria M.;Gallinger, Steven;Hruban, Ralph H.;Maitra, Anirban;Iacobuzio-Donahue, Christine A.;Schulick, Richard D.;Wolfgang, Christopher L.;Morgan, Richard A.;Lawlor, Rita T.;Capelli, Paola;Corbo, Vincenzo;Scardoni, Maria;Tortora, Giampaolo;Tempero, Margaret A.;Mann, Karen M.;Jenkins, Nancy A.;Perez-Mancera, Pedro A.;Adams, David J.;Largaespada, David A.;Wessels, Lodewyk F. A.;Rust, Alistair G.;Stein, Lincoln D.;Tuveson, David A.;Copeland, Neal G.;Musgrove, Elizabeth A.;Scarpa, Aldo;Eshleman, James R.;Hudson, Thomas J.;Sutherland, Robert L.;Wheeler, David A.;Pearson, John V.;McPherson, John D.;Gibbs, Richard A.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.