A renal cell carcinoma tumorgraft platform to advance precision medicine.

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.

Cell reports. 2021 Nov 23 [Epub]

Roy Elias, Vanina T Tcheuyap, Akash K Kaushik, Nirmish Singla, Ming Gao, Oscar Reig Torras, Alana Christie, Aditi Mulgaonkar, Layton Woolford, Christina Stevens, Kavitha Priya Kettimuthu, Andrea Pavia-Jimenez, Lindsey K Boroughs, Allison Joyce, Marianna Dakanali, Hollis Notgrass, Vitaly Margulis, Jeffrey A Cadeddu, Ivan Pedrosa, Noelle S Williams, Xiankai Sun, Ralph J DeBerardinis, Orhan K Öz, Hua Zhong, Somasekar Seshagiri, Zora Modrusan, Brandi L Cantarel, Payal Kapur, James Brugarolas

Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Howard Hughes Medical Institute and Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Division of Biostatistics, Department of Clinical Sciences, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Bioinformatics, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Howard Hughes Medical Institute and Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Bioinformatics, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Microchemistry, Proteomics, Lipidomics and NGS, Genentech, Inc., South San Francisco, CA, USA., Department of Bioinformatics, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: .

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