@article{870c046330dd4d78814af52c3ee44a3f,
title = "Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts",
abstract = "Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.",
author = "{PDXNET Consortium} and {EurOPDX Consortium} and Woo, {Xing Yi} and Jessica Giordano and Anuj Srivastava and Zhao, {Zi Ming} and Lloyd, {Michael W.} and {de Bruijn}, Roebi and Suh, {Yun Suhk} and Rajesh Patidar and Li Chen and Sandra Scherer and Bailey, {Matthew H.} and Yang, {Chieh Hsiang} and Emilio Cortes-Sanchez and Yuanxin Xi and Jing Wang and Jayamanna Wickramasinghe and Kossenkov, {Andrew V.} and Rebecca, {Vito W.} and Hua Sun and Mashl, {R. Jay} and Davies, {Sherri R.} and Ryan Jeon and Christian Frech and Jelena Randjelovic and Jacqueline Rosains and Francesco Galimi and Andrea Bertotti and Adam Lafferty and O{\textquoteright}Farrell, {Alice C.} and Elodie Modave and Diether Lambrechts and {ter Brugge}, Petra and Violeta Serra and Elisabetta Marangoni and {El Botty}, Rania and Li Ding and Shunqiang Li and Ramaswamy Govindan and Song Cao and Feng Chen and DiPersio, {John F.} and Ma, {Cynthia X.} and {Van Tine}, {Brian A.} and Andrea Wang-Gillam and Wendl, {Michael C.} and Wyczalkowski, {Matthew A.} and Aft, {Rebecca L.} and Fields, {Ryan C.} and Jingqin Luo and Fuh, {Katherine C.}",
note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2021",
month = jan,
doi = "10.1038/s41588-020-00750-6",
language = "English",
volume = "53",
pages = "86--99",
journal = "Nature Genetics",
issn = "1061-4036",
number = "1",
}