학술논문
Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer
Document Type
article
Author
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
Source
Nature Communications, Vol 14, Iss 1, Pp 1-16 (2023)
Subject
Language
English
ISSN
2041-1723
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.