A renal cell carcinoma tumorgraft platform to advance precision medicine

Renal cell carcinoma (RCC) encompasses a heterogenous group of diseases, creating challenges for drug development. Preclinical models which are both translatable and representative of disease heterogeneity are needed. Patient-derived xenograft (PDX) or tumorgraft (TG) models recapitulate the biology and treatment responsiveness of RCC. Through the orthotopic implantation into NOD/SCID mice of tumor samples from >900 ethnically-diverse patients at UT Southwestern Medical Center and the affiliated county hospital, we have generated a resource comprising 172 independently-derived stably-engrafted TG lines from 148 patients. The lines have been characterized histologically and genomically (whole exome sequencing [n = 97] and RNA sequencing [n =102]). They represent a variety of histological and on
cogenotypes including representative TCGA clades further validated through orthogonal metabolomic analyses in a subset. We illustrate how this platform has enabled a deeper understanding of the biology and molecular genetics of RCC, the development of both tissue- and imaging-based biomarkers, as well as advances in drug development. This resource expands the diversity of models available to the scientific community to advance precision diagnosis and therapy in RCC.EGA study EGAS00001005516