Nature Communications (Nov 2023)
Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer
- Funan He,
- Abhik M. Bandyopadhyay,
- Laura J. Klesse,
- Anna Rogojina,
- Sang H. Chun,
- Erin Butler,
- Taylor Hartshorne,
- Trevor Holland,
- Dawn Garcia,
- Korri Weldon,
- Luz-Nereida Perez Prado,
- Anne-Marie Langevin,
- Allison C. Grimes,
- Aaron Sugalski,
- Shafqat Shah,
- Chatchawin Assanasen,
- Zhao Lai,
- Yi Zou,
- Dias Kurmashev,
- Lin Xu,
- Yang Xie,
- Yidong Chen,
- Xiaojing Wang,
- Gail E. Tomlinson,
- Stephen X. Skapek,
- Peter J. Houghton,
- Raushan T. Kurmasheva,
- Siyuan Zheng
Affiliations
- Funan He
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Abhik M. Bandyopadhyay
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Laura J. Klesse
- Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center
- Anna Rogojina
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Sang H. Chun
- Department of Biochemistry and Structural Biology, University of Texas Health Science Center
- Erin Butler
- Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center
- Taylor Hartshorne
- Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center
- Trevor Holland
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Dawn Garcia
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Korri Weldon
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Luz-Nereida Perez Prado
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Anne-Marie Langevin
- Department of Pediatrics, University of Texas Health Science Center
- Allison C. Grimes
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Aaron Sugalski
- Department of Pediatrics, University of Texas Health Science Center
- Shafqat Shah
- Department of Pediatrics, University of Texas Health Science Center
- Chatchawin Assanasen
- Department of Pediatrics, University of Texas Health Science Center
- Zhao Lai
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Yi Zou
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Dias Kurmashev
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Lin Xu
- Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center
- Yang Xie
- Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center
- Yidong Chen
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Xiaojing Wang
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Gail E. Tomlinson
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Stephen X. Skapek
- Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center
- Peter J. Houghton
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Raushan T. Kurmasheva
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- Siyuan Zheng
- Greehey Children’s Cancer Research Institute, University of Texas Health Science Center
- DOI
- https://doi.org/10.1038/s41467-023-43373-1
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 16
Abstract
Abstract Subcutaneous patient-derived xenografts (PDXs) are an important tool for childhood cancer research. Here, we describe a resource of 68 early passage PDXs established from 65 pediatric solid tumor patients. Through genomic profiling of paired PDXs and patient tumors (PTs), we observe low mutational similarity in about 30% of the PT/PDX pairs. Clonal analysis in these pairs show an aggressive PT minor subclone seeds the major clone in the PDX. We show evidence that this subclone is more immunogenic and is likely suppressed by immune responses in the PT. These results suggest interplay between intratumoral heterogeneity and antitumor immunity may underlie the genetic disparity between PTs and PDXs. We further show that PDXs generally recapitulate PTs in copy number and transcriptomic profiles. Finally, we report a gene fusion LRPAP1-PDGFRA. In summary, we report a childhood cancer PDX resource and our study highlights the role of immune constraints on tumor evolution.
