Orthotopic patient-derived xenografts of paediatric solid tumours.
Orthotopic patient-derived xenografts of paediatric solid tumours.
复制标题
DOI：
10.1038/nature23647
复制
发表时间：
2017-09-07
期刊：
影响因子：
64.8
通讯作者：
Dyer MA
中科院分区：
文献类型：
--
作者：
Stewart E;Federico SM;Chen X;Shelat AA;Bradley C;Gordon B;Karlstrom A;Twarog NR;Clay MR;Bahrami A;Freeman BB 3rd;Xu B;Zhou X;Wu J;Honnell V;Ocarz M;Blankenship K;Dapper J;Mardis ER;Wilson RK;Downing J;Zhang J;Easton J;Pappo A;Dyer MA
儿童实体瘤起源于内胚层、外胚层或中胚层谱系。尽管实体瘤儿童的总体存活率为75%，但复发疾病儿童的存活率低于30%。为了捕捉儿童实体肿瘤的复杂性和多样性，并建立新的复发疾病模型，我们开发了一种在诊断、复发和尸检时产生原位患者来源的异种移植物(O-PDX)的方案。从168例患者的肿瘤标本中，建立了针对12种癌症的67个O-PDX。O-PDX肿瘤的起源反映在它们的基因表达谱和表观基因组中。对肿瘤进行基因组图谱分析，包括详细的克隆分析，以确定异种移植中的克隆群体是否重现了患者的肿瘤。我们发现了几种药物的脆弱性，并表明WEE1抑制剂(AZD1775)、伊立替康和长春新碱的组合可以在体内导致对多发性横纹肌肉瘤O-PDX肿瘤的完全反应。
Pediatric solid tumors arise from endodermal, ectodermal, or mesodermal lineages. Although the overall survival of children with solid tumors is 75%, that of children with recurrent disease is below 30%. To capture the complexity and diversity of pediatric solid tumors and establish new models of recurrent disease, we developed a protocol to produce orthotopic patient-derived xenografts (O-PDXs) at diagnosis, recurrence, and autopsy. Tumor specimens were received from 168 patients, and 67 O-PDXs were established for 12 types of cancer. The origins of the O-PDX tumors were reflected in their gene-expression profiles and epigenomes. Genomic profiling of the tumors, including detailed clonal analysis, was performed to determine whether the clonal population in the xenograft recapitulated the patient’s tumor. We identified several drug vulnerabilities and showed that the combination of a WEE1 inhibitor (AZD1775), irinotecan, and vincristine can lead to complete response in multiple rhabdomyosarcoma O-PDX tumors in vivo.
登录
查看更多内容
影响因子：
82.9
作者：
Gao, Hui;Korn, Joshua M.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
64.5
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
通讯作者：
Chen Y
影响因子：
64.5
作者：
van de Wetering M;Francies HE;Francis JM;Bounova G;Iorio F;Pronk A;van Houdt W;van Gorp J;Taylor-Weiner A;Kester L;McLaren-Douglas A;Blokker J;Jaksani S;Bartfeld S;Volckman R;van Sluis P;Li VS;Seepo S;Sekhar Pedamallu C;Cibulskis K;Carter SL;McKenna A;Lawrence MS;Lichtenstein L;Stewart C;Koster J;Versteeg R;van Oudenaarden A;Saez-Rodriguez J;Vries RG;Getz G;Wessels L;Stratton MR;McDermott U;Meyerson M;Garnett MJ;Clevers H
通讯作者：
Clevers H
影响因子：
8.8
作者：
Chen X;Bahrami A;Pappo A;Easton J;Dalton J;Hedlund E;Ellison D;Shurtleff S;Wu G;Wei L;Parker M;Rusch M;Nagahawatte P;Wu J;Mao S;Boggs K;Mulder H;Yergeau D;Lu C;Ding L;Edmonson M;Qu C;Wang J;Li Y;Navid F;Daw NC;Mardis ER;Wilson RK;Downing JR;Zhang J;Dyer MA;St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project
通讯作者：
St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y