A renal cell carcinoma tumorgraft platform to advance precision medicine
Roy Elias, Vanina Toffessi Tcheuyap, Akash Kaushik, Nirmish Singla, Ming Gao, Oscar Reig Torras, Alana Christie, Aditi Mulgaonkar, Layton Woolford, Christina Stevens, Kavitha Priya Kettimuthu, Andrea Pavía-Jiménez, Lindsey K. Boroughs, Allison Joyce, Marianna Dakanali, Hollis Notgrass, Vitaly Margulis, Jeffrey A. Cadeddu, Iván Pedrosa, Noelle S. Williams, Xiankai Sun, Ralph J. DeBerardinis, Orhan K. Öz, Hua Zhong, Somasekar Seshagiri, Zora Modrušan, Brandi L. Cantarel, Payal Kapur, James Brugarolas
Abstract
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.