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. 2021 Jan;53(1):86-99.
doi: 10.1038/s41588-020-00750-6. Epub 2021 Jan 7.

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Xing Yi Woo #  1 , Jessica Giordano #  2   3 , Anuj Srivastava  1 , Zi-Ming Zhao  1 , Michael W Lloyd  4 , Roebi de Bruijn  5 , Yun-Suhk Suh  6 , Rajesh Patidar  7 , Li Chen  7 , Sandra Scherer  8 , Matthew H Bailey  8   9 , Chieh-Hsiang Yang  8 , Emilio Cortes-Sanchez  8 , Yuanxin Xi  10 , Jing Wang  10 , Jayamanna Wickramasinghe  11 , Andrew V Kossenkov  11 , Vito W Rebecca  11 , Hua Sun  12 , R Jay Mashl  12 , Sherri R Davies  12 , Ryan Jeon  13 , Christian Frech  13 , Jelena Randjelovic  13 , Jacqueline Rosains  13 , Francesco Galimi  2   3 , Andrea Bertotti  2   3 , Adam Lafferty  14 , Alice C O'Farrell  14 , Elodie Modave  15   16 , Diether Lambrechts  15   16 , Petra Ter Brugge  5 , Violeta Serra  17 , Elisabetta Marangoni  18 , Rania El Botty  18 , Hyunsoo Kim  1 , Jong-Il Kim  6 , Han-Kwang Yang  6 , Charles Lee  1   19   20 , Dennis A Dean 2nd  13 , Brandi Davis-Dusenbery  13 , Yvonne A Evrard  7 , James H Doroshow  21 , Alana L Welm  8 , Bryan E Welm  8   22 , Michael T Lewis  23 , Bingliang Fang  24 , Jack A Roth  24 , Funda Meric-Bernstam  25 , Meenhard Herlyn  11 , Michael A Davies  26 , Li Ding  12 , Shunqiang Li  12 , Ramaswamy Govindan  12 , Claudio Isella  2   3 , Jeffrey A Moscow  27 , Livio Trusolino  2   3 , Annette T Byrne  14 , Jos Jonkers  5 , Carol J Bult  4 , Enzo Medico  28   29 , Jeffrey H Chuang  30 ; PDXNET Consortium; EurOPDX Consortium
Collaborators, Affiliations
Free PMC article

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Xing Yi Woo et al. Nat Genet. 2021 Jan.
Free PMC article

Erratum in

  • Author Correction: Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts.
    Woo XY, Giordano J, Srivastava A, Zhao ZM, Lloyd MW, de Bruijn R, Suh YS, Patidar R, Chen L, Scherer S, Bailey MH, Yang CH, Cortes-Sanchez E, Xi Y, Wang J, Wickramasinghe J, Kossenkov AV, Rebecca VW, Sun H, Mashl RJ, Davies SR, Jeon R, Frech C, Randjelovic J, Rosains J, Galimi F, Bertotti A, Lafferty A, O'Farrell AC, Modave E, Lambrechts D, Ter Brugge P, Serra V, Marangoni E, El Botty R, Kim H, Kim JI, Yang HK, Lee C, Dean DA 2nd, Davis-Dusenbery B, Evrard YA, Doroshow JH, Welm AL, Welm BE, Lewis MT, Fang B, Roth JA, Meric-Bernstam F, Herlyn M, Davies MA, Ding L, Li S, Govindan R, Isella C, Moscow JA, Trusolino L, Byrne AT, Jonkers J, Bult CJ, Medico E, Chuang JH; PDXNET Consortium; EurOPDX Consortium. Woo XY, et al. Nat Genet. 2021 May;53(5):761. doi: 10.1038/s41588-021-00811-4. Nat Genet. 2021. PMID: 33608693 Free PMC article. No abstract available.

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.

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