Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts.
Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts.
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DOI：
10.1016/j.celrep.2013.08.022
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发表时间：
2013-09-26
期刊：
影响因子：
8.8
通讯作者：
Ellis MJ
中科院分区：
文献类型：
--
作者：
Li S;Shen D;Shao J;Crowder R;Liu W;Prat A;He X;Liu S;Hoog J;Lu C;Ding L;Griffith OL;Miller C;Larson D;Fulton RS;Harrison M;Mooney T;McMichael JF;Luo J;Tao Y;Goncalves R;Schlosberg C;Hiken JF;Saied L;Sanchez C;Giuntoli T;Bumb C;Cooper C;Kitchens RT;Lin A;Phommaly C;Davies SR;Zhang J;Kavuri MS;McEachern D;Dong YY;Ma C;Pluard T;Naughton M;Bose R;Suresh R;McDowell R;Michel L;Aft R;Gillanders W;DeSchryver K;Wilson RK;Wang S;Mills GB;Gonzalez-Angulo A;Edwards JR;Maher C;Perou CM;Mardis ER;Ellis MJ
为了表征用于功能研究的患者来源的异种移植物（PDX），我们与代表主要内在亚型的起源乳腺癌进行了全基因组比较。发现结构和拷贝数畸变以高保真度保留。然而，在单核苷酸水平上，记录了不同数量的PDX特异性体细胞事件，尽管它们很少具有功能意义。变异等位基因频率通常保留在PDX中，表明克隆代表性可以移植。雌激素受体阳性PDX与ESR 1配体结合域突变、基因扩增或ESR 1/YAP 1易位相关。这些事件在人体、细胞系和PDX内分泌反应研究中产生了不同的内分泌治疗反应表型。因此，深度测序的PDX模型是寻找基因组正向治疗选择和捕获标准细胞系中未观察到的内分泌耐药病因的重要资源。原始肿瘤基因组为评估移植后的遗传漂变和克隆代表性提供了基准。
To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
3.7
作者：
Ortega-Recalde O;Vergara JI;Fonseca DJ;Ríos X;Mosquera H;Bermúdez OM;Medina CL;Vargas CI;Pallares AE;Restrepo CM;Laissue P
通讯作者：
Laissue P
影响因子：
64.8
作者：
Matsushita, Hirokazu;Vesely, Matthew D.;Koboldt, Daniel C.;Rickert, Charles G.;Uppaluri, Ravindra;Magrini, Vincent J.;Arthur, Cora D.;White, J. Michael;Chen, Yee-Shiuan;Shea, Lauren K.;Hundal, Jasreet;Wendl, Michael C.;Demeter, Ryan;Wylie, Todd;Allison, James P.;Smyth, Mark J.;Old, Lloyd J.;Mardis, Elaine R.;Schreiber, Robert D.
通讯作者：
Schreiber, Robert D.
影响因子：
9.2
作者：
Gelman, Irwin H.
通讯作者：
Gelman, Irwin H.