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

doi:10.1016/j.celrep.2021.110055

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 journal › Article › peer-review

18 Scopus citations

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 language	English (US)
Article number	110055
Journal	Cell Reports
Volume	37
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2021.110055
State	Published - 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

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2021.110055

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Elias, R., Tcheuyap, V. T., Kaushik, A. K., Singla, N., Gao, M., Reig Torras, O., Christie, A., Mulgaonkar, A., Woolford, L., Stevens, C., Kettimuthu, K. P., Pavia-Jimenez, A., Boroughs, L. K., Joyce, A., Dakanali, M., Notgrass, H., Margulis, V., Cadeddu, J. A., Pedrosa, I., ... Brugarolas, J. (2021). A renal cell carcinoma tumorgraft platform to advance precision medicine. Cell Reports, 37(8), Article 110055. https://doi.org/10.1016/j.celrep.2021.110055

Elias, R, Tcheuyap, VT, Kaushik, AK, Singla, N, Gao, M, Reig Torras, O, Christie, A, Mulgaonkar, A, Woolford, L, Stevens, C, Kettimuthu, KP, Pavia-Jimenez, A, Boroughs, LK, Joyce, A, Dakanali, M, Notgrass, H, Margulis, V , Cadeddu, JA , Pedrosa, I , Williams, NS , Sun, X , DeBerardinis, RJ , Öz, OK, Zhong, H, Seshagiri, S, Modrusan, Z, Cantarel, BL, Kapur, P & Brugarolas, J 2021, 'A renal cell carcinoma tumorgraft platform to advance precision medicine', Cell Reports, vol. 37, no. 8, 110055. https://doi.org/10.1016/j.celrep.2021.110055

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title = "A renal cell carcinoma tumorgraft platform to advance precision medicine",

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.",

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",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = nov,

day = "23",

doi = "10.1016/j.celrep.2021.110055",

language = "English (US)",

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AU - Elias, Roy

AU - Tcheuyap, Vanina T.

AU - Kaushik, Akash K.

AU - Singla, Nirmish

AU - Gao, Ming

AU - Reig Torras, Oscar

AU - Christie, Alana

AU - Mulgaonkar, Aditi

AU - Woolford, Layton

AU - Stevens, Christina

AU - Kettimuthu, Kavitha Priya

AU - Pavia-Jimenez, Andrea

AU - Boroughs, Lindsey K.

AU - Joyce, Allison

AU - Dakanali, Marianna

AU - Notgrass, Hollis

AU - Margulis, Vitaly

AU - Cadeddu, Jeffrey A.

AU - Pedrosa, Ivan

AU - Williams, Noelle S.

AU - Sun, Xiankai

AU - DeBerardinis, Ralph J.

AU - Öz, Orhan K.

AU - Zhong, Hua

AU - Seshagiri, Somasekar

AU - Modrusan, Zora

AU - Cantarel, Brandi L.

AU - Kapur, Payal

AU - Brugarolas, James

PY - 2021/11/23

Y1 - 2021/11/23

N2 - 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.

AB - 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.

KW - BAP1

KW - HIF

KW - NGS

KW - PET

KW - PT2385

KW - TAK-243

KW - VHL

KW - animal models

KW - belzutifan

KW - biomarkers

KW - iPET

KW - immunoPET

KW - kidney cancer

KW - metabolomics

KW - molecular imaging

KW - patient-derived xenograft

KW - radiotracer

KW - renal cell carcinoma

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DO - 10.1016/j.celrep.2021.110055

M3 - Article

C2 - 34818533

AN - SCOPUS:85119493156

SN - 2211-1247

VL - 37

JO - Cell Reports

JF - Cell Reports

IS - 8

M1 - 110055

ER -

A renal cell carcinoma tumorgraft platform to advance precision medicine

Abstract

Keywords

ASJC Scopus subject areas

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