A renal cell carcinoma tumorgraft platform to advance precision medicine

肾细胞癌肿瘤移植平台助力精准医疗

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作者: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, Je

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.

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