Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts
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Published:2021-01
Issue:1
Volume:53
Page:86-99
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ISSN:1061-4036
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Container-title:Nature Genetics
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language:en
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Short-container-title:Nat Genet
Author:
Woo Xing YiORCID, , Giordano JessicaORCID, Srivastava Anuj, Zhao Zi-Ming, Lloyd Michael W., de Bruijn Roebi, Suh Yun-Suhk, Patidar Rajesh, Chen Li, Scherer Sandra, Bailey Matthew H., Yang Chieh-Hsiang, Cortes-Sanchez Emilio, Xi Yuanxin, Wang JingORCID, Wickramasinghe Jayamanna, Kossenkov Andrew V., Rebecca Vito W., Sun Hua, Mashl R. Jay, Davies Sherri R.ORCID, Jeon Ryan, Frech Christian, Randjelovic Jelena, Rosains Jacqueline, Galimi Francesco, Bertotti Andrea, Lafferty Adam, O’Farrell Alice C.ORCID, Modave Elodie, Lambrechts DietherORCID, ter Brugge Petra, Serra VioletaORCID, Marangoni ElisabettaORCID, El Botty Rania, Kim Hyunsoo, Kim Jong-IlORCID, Yang Han-Kwang, Lee Charles, Dean Dennis A.ORCID, Davis-Dusenbery Brandi, Evrard Yvonne A.ORCID, Doroshow James H., Welm Alana L.ORCID, Welm Bryan E., Lewis Michael T., Fang Bingliang, Roth Jack A.ORCID, Meric-Bernstam Funda, Herlyn MeenhardORCID, Davies Michael A.ORCID, Ding Li, Li Shunqiang, Govindan Ramaswamy, Isella Claudio, Moscow Jeffrey A.ORCID, Trusolino LivioORCID, Byrne Annette T., Jonkers JosORCID, Bult Carol J., Medico EnzoORCID, Chuang Jeffrey H.ORCID,
Abstract
AbstractPatient-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.
Publisher
Springer Science and Business Media LLC
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