A renal cell carcinoma tumorgraft platform to advance precision medicine

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. WilliamsXiankai Sun, Ralph J. DeBerardinis, Orhan K. Öz, Hua Zhong, Somasekar Seshagiri, Zora Modrusan, Brandi L. Cantarel, Payal Kapur, James Brugarolas

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number110055
JournalCell Reports
Volume37
Issue number8
DOIs
StatePublished - Nov 23 2021

Keywords

  • BAP1
  • HIF
  • NGS
  • PET
  • PT2385
  • TAK-243
  • VHL
  • animal models
  • belzutifan
  • biomarkers
  • iPET
  • immunoPET
  • kidney cancer
  • metabolomics
  • molecular imaging
  • patient-derived xenograft
  • radiotracer
  • renal cell carcinoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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