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Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment

Hua Sun, Song Cao, R. Jay Mashl, Chia-Kuei Mo, Simone Zaccaria, Michael C. Wendl, Sherri R. Davies, Matthew H. Bailey, Tina M. Primeau, Jeremy Hoog, Jacqueline L. Mudd, Dennis A. Dean (+148 others)
2021 Nature Communications  

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AbstractDevelopment of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic
more » ... driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs' recapitulation of human tumors.
doi:10.1038/s41467-021-25177-3 pmid:34429404 pmcid:PMC8384880 fatcat:t53uwnhuszbcfhsh734gh4yioy
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Hua Sun, Song Cao, R. Jay Mashl, Chia-Kuei Mo, Simone Zaccaria, Michael C. Wendl, Sherri R. Davies, Matthew H. Bailey, Tina M. Primeau, Jeremy Hoog, Jacqueline L. Mudd, Dennis A. Dean, Rajesh Patidar, Li Chen, Matthew A. Wyczalkowski, Reyka G. Jayasinghe, Fernanda Martins Rodrigues, Nadezhda V. Terekhanova, Yize Li, Kian-Huat Lim, Andrea Wang-Gillam, Brian A. Van Tine, Cynthia X. Ma, Rebecca Aft, Katherine C. Fuh, Julie K. Schwarz, Jose P. Zevallos, Sidharth V. Puram, John F. Dipersio, Julie Belmar, Jason Held, Jingqin Luo, Brian A. Van Tine, Rose Tipton, Yige Wu, Lijun Yao, Daniel Cui Zhou, Andrew Butterfield, Zhengtao Chu, Maihi Fujita, Chieh-Hsiang Yang, Emilio Cortes-Sanchez, Sandra Scherer, Ling Zhao, Tijana Borovski, Vicki Chin, John DiGiovanna, Christian Frech, Jeffrey Grover, Ryan Jeon, Soner Koc, Jelena Randjelovic, Sara Seepo, Tamara Stankovic, Lacey E. Dobrolecki, Michael Ittmann, Susan G. Hilsenbeck, Bert W. O'Malley, Nicholas Mitsiades, Salma Kaochar, Argun Akcakanat, Jithesh Augustine, Huiqin Chen, Bingbing Dai, Kurt W. Evans, Kelly Gale, Don Gibbons, Min Jin Ha, Vanessa Jensen, Michael Kim, Bryce P. Kirby, Scott Kopetz, Christopher D. Lanier, Dali Li, Mourad Majidi, David Menter, Ismail Meraz, Turcin Saridogan, Stephen Scott, Alexey Sorokin, Coya Tapia, Jing Wang, Shannon Westin, Yuanxin Xi, Yi Xu, Fei Yang, Timothy A. Yap, Vashisht G. Yennu-Nanda, Erkan Yuca, Jianhua Zhang, Ran Zhang, Xiaoshan Zhang, Xiaofeng Zheng, Dylan Fingerman, Haiyin Lin, Qin Liu, Andrew V. Kossenkov, Vito W. Rebecca, Rajasekharan Somasundaram, Michae T. Tetzlaff, Jayamanna Wickramasinghe, Min Xiao, Xiaowei Xu, Carol J. Bult, Peter N. Robinson, Anuj Srivastava, Michael W. Lloyd, Steven B. Neuhauser, Jill Rubinstein, Brian J. Sanderson, Brian White, Xing Yi Woo, Tiffany Wallace, John D. Minna, Gao Boning, Luc Girard, Hyunsil Park, Brenda C. Timmons, Katherine L. Nathanson, George Xu, Chong-xian Pan, Moon S. Chen Jr, Luis G. Carvajal-Carmona, May Cho, Nicole B. Coggins, Ralph W. deVere White, Guadalupe Polanco-Echeverry, Ana Estrada, David R. Gandara, Amanda R. Kirane, Tiffany Le, Paul Lott, Alexa Morales Arana, Jonathan W. Reiss, Sienna Rocha, Clifford G. Tepper, Ted Toal, Hongyong Zhang, Ai-Hong Ma, Brandi Davis-Dusenbery, Matthew J. Ellis, Michael T. Lewis, Michael A. Davies, Meenhard Herlyn, Bingliang Fang, Jack A. Roth, Alana L. Welm, Bryan E. Welm, Funda Meric-Bernstam, Feng Chen, Ryan C. Fields, Shunqiang Li, Ramaswamy Govindan, James H. Doroshow, Jeffrey A. Moscow, Yvonne A. Evrard, Jeffrey H. Chuang, Benjamin J. Raphael, Li Ding, The NCI PDXNet Consortium. "Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment." Nature Communications 12.1 (2021) 5086