| Literature DB >> 33414553 |
Xing Yi Woo1, Jessica Giordano2,3, Anuj Srivastava1, Zi-Ming Zhao1, Michael W Lloyd4, Roebi de Bruijn5, Yun-Suhk Suh6, Rajesh Patidar7, Li Chen7, Sandra Scherer8, Matthew H Bailey8,9, Chieh-Hsiang Yang8, Emilio Cortes-Sanchez8, Yuanxin Xi10, Jing Wang10, Jayamanna Wickramasinghe11, Andrew V Kossenkov11, Vito W Rebecca11, Hua Sun12, R Jay Mashl12, Sherri R Davies12, Ryan Jeon13, Christian Frech13, Jelena Randjelovic13, Jacqueline Rosains13, Francesco Galimi2,3, Andrea Bertotti2,3, Adam Lafferty14, Alice C O'Farrell14, Elodie Modave15,16, Diether Lambrechts15,16, Petra Ter Brugge5, Violeta Serra17, Elisabetta Marangoni18, Rania El Botty18, Hyunsoo Kim1, Jong-Il Kim6, Han-Kwang Yang6, Charles Lee1,19,20, Dennis A Dean13, Brandi Davis-Dusenbery13, Yvonne A Evrard7, James H Doroshow21, Alana L Welm8, Bryan E Welm8,22, Michael T Lewis23, Bingliang Fang24, Jack A Roth24, Funda Meric-Bernstam25, Meenhard Herlyn11, Michael A Davies26, Li Ding12, Shunqiang Li12, Ramaswamy Govindan12, Claudio Isella2,3, Jeffrey A Moscow27, Livio Trusolino2,3, Annette T Byrne14, Jos Jonkers5, Carol J Bult4, Enzo Medico28,29, Jeffrey H Chuang30.
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.Entities:
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Year: 2021 PMID： 33414553 PMCID： PMC7808565 DOI： 10.1038/s41588-020-00750-6
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330