A renal cell carcinoma tumorgraft platform to advance precision medicine

被引：33

作者：

Elias, Roy ^{[1
,2
,13
]}

Tcheuyap, Vanina T. ^{[1
]}

Kaushik, Akash K. ^{[3
,4
]}

Singla, Nirmish ^{[1
,5
,14
,15
]}

Gao, Ming ^{[1
]}

Torras, Oscar Reig ^{[1
,16
,17
]}

Christie, Alana ^{[1
,6
]}

Mulgaonkar, Aditi ^{[7
]}

Woolford, Layton ^{[1
]}

Stevens, Christina ^{[1
]}

Kettimuthu, Kavitha Priya ^{[8
]}

Pavia-Jimenez, Andrea ^{[1
]}

Boroughs, Lindsey K. ^{[3
,4
,18
]}

Joyce, Allison ^{[1
]}

Dakanali, Marianna ^{[7
]}

Notgrass, Hollis ^{[9
]}

Margulis, Vitaly ^{[1
,5
]}

Cadeddu, Jeffrey A. ^{[1
,5
]}

Pedrosa, Ivan ^{[1
,7
,10
]}

Williams, Noelle S. ^{[1
,11
]}

Sun, Xiankai ^{[1
,7
,10
]}

DeBerardinis, Ralph J. ^{[1
,3
,4
]}

Oz, Orhan K. ^{[1
,7
]}

Zhong, Hua ^{[9
,11
]}

Seshagiri, Somasekar ^{[12
,19
]}

Modrusan, Zora ^{[12
]}

Cantarel, Brandi L. ^{[11
]}

Kapur, Payal ^{[1
,5
,9
]}

Brugarolas, James ^{[1
,2
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Simmons Comprehens Canc Ctr, Kidney Canc Program, Dallas, TX 75390 USA

[2] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA

[3] Univ Texas Southwestern Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

[4] Univ Texas Southwestern Med Ctr Dallas, Res Inst, Childrens Med Ctr, Dallas, TX 75390 USA

[5] Univ Texas Southwestern Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA

[6] Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Div Biostat, Dallas, TX 75390 USA

[7] Univ Texas Southwestern Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA

[8] Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[9] Univ Texas Southwestern Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA

[10] Univ Texas Southwestern Med Ctr Dallas, Adv Imaging Res Ctr, Dallas, TX 75390 USA

[11] Univ Texas Southwestern Med Ctr Dallas, Dept Bioinformat, Dallas, TX 75390 USA

[12] Genentech Inc, Dept Microchem Prote Lipid & NGS, San Francisco, CA 94080 USA

[13] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, 401 N Broadway, Baltimore, MD 21231 USA

[14] Johns Hopkins Univ, Dept Urol, James Buchanan Brady Urol Inst, Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA

[15] Johns Hopkins Univ, Dept Oncol, James Buchanan Brady Urol Inst, Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA

[16] Hosp Clin Barcelona, Dept Oncol, C Villarroel 170, Barcelona, Spain

[17] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Translat Genom & Targeted Therapeut Solid Tumors, C Villarroel 170, Barcelona, Spain

[18] Bristol Myers Squibb, 4931 George Rd, Tampa, FL 33634 USA

[19] SciGenom Res Fdn, Bangalore, Karnataka, India

来源：

CELL REPORTS | 2021年 / 37卷 / 08期

基金：

美国国家卫生研究院;

关键词：

COMPREHENSIVE MOLECULAR CHARACTERIZATION; PRECLINICAL MODELS; INTERFERON-ALPHA; PLUS AXITINIB; SUNITINIB; DNA; ANTAGONIST; TRIAL; BAP1; XENOGRAFTS;

D O I：

10.1016/j.celrep.2021.110055

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Renal cell carcinoma (RCC) encompasses a heterogenous group of tumors, but representative preclinical models are lacking. We previously showed that patient-derived tumorgraft (TG) models recapitulate the biology and treatment responsiveness. Through systematic orthotopic implantation of tumor samples from 926 ethnically diverse individuals into non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice, we generate a resource comprising 172 independently derived, stably engrafted TG lines from 148 individuals. TG lines are characterized histologically and genomically (whole-exome [n = 97] and RNA [n = 102] sequencing). The platform features a variety of histological and oncogenotypes, including TCGA clades further corroborated through orthogonal metabolomic analyses. We illustrate how it enables a deeper understanding of RCC biology; enables the development of tissue-and imaging-based molecular probes; and supports advances in drug development.

引用

页数：22

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