Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment
Hua Sun(James S. McDonnell Foundation), Song Cao(James S. McDonnell Foundation), R. Jay Mashl(James S. McDonnell Foundation), Chia-Kuei Mo(James S. McDonnell Foundation), Simone Zaccaria(Princeton University), Michael C. Wendl(James S. McDonnell Foundation), Sherri R. Davies(Washington University in St. Louis), Matthew H. Bailey(University of Utah), Tina Primeau(Washington University in St. Louis), Jeremy Hoog(Washington University in St. Louis), Jacqueline L. Mudd(Washington University in St. Louis), Dennis A. Dean(Seven Bridges Genomics (United States)), Rajesh Patidar(Frederick National Laboratory for Cancer Research), Li Chen(Frederick National Laboratory for Cancer Research), Matthew A. Wyczalkowski(James S. McDonnell Foundation), Reyka G. Jayasinghe(James S. McDonnell Foundation), Fernanda Martins Rodrigues(James S. McDonnell Foundation), Nadezhda V. Terekhanova(James S. McDonnell Foundation), Yize Li(James S. McDonnell Foundation), Kian‐Huat Lim(Washington University in St. Louis), Andrea Wang‐Gillam(Washington University in St. Louis), Brian A. Van Tine(Washington University in St. Louis), X. Cynthia(Washington University in St. Louis), Rebecca Aft(Washington University in St. Louis), Katherine C. Fuh(Washington University in St. Louis), Julie K. Schwarz(Washington University in St. Louis), José P. Zevallos(Washington University in St. Louis), Sidharth V. Puram(Washington University in St. Louis), John F. DiPersio(Washington University in St. Louis), Julie Belmar(Washington University in St. Louis), Jason M. Held(Washington University in St. Louis), Jingqin Luo(Washington University in St. Louis), Brian A. Van Tine(Washington University in St. Louis), Rose Tipton(Washington University in St. Louis), Yige Wu(James S. McDonnell Foundation), Lijun Yao(James S. McDonnell Foundation), Daniel Cui Zhou(James S. McDonnell Foundation), Andrew Butterfield(University of Utah), Zhengtao Chu(University of Utah), Maihi Fujita(University of Utah), Chieh‐Hsiang Yang(University of Utah), Emilio Cortes-Sanchez(University of Utah), Sandra D. Scherer(University of Utah), Ling Zhao(University of Utah), Tijana Borovski(Seven Bridges Genomics (United States)), Vicki Chin(Seven Bridges Genomics (United States)), John J. DiGiovanna(Seven Bridges Genomics (United States)), Christian Frech(Seven Bridges Genomics (United States)), Jeffrey Grover(Seven Bridges Genomics (United States)), Ryan Jeon(Seven Bridges Genomics (United States)), Soner Koc(Seven Bridges Genomics (United States)), Jelena Randjelović(Seven Bridges Genomics (United States)), Sara Seepo(Seven Bridges Genomics (United States)), Tamara Stanković(Seven Bridges Genomics (United States)), Lacey E. Dobrolecki(Baylor College of Medicine), Michael Ittmann(Baylor College of Medicine), Susan G. Hilsenbeck(Baylor College of Medicine), Bert W. O’Malley(Baylor College of Medicine), Nicholas Mitsiades(Baylor College of Medicine), Salma Kaochar(Baylor College of Medicine), Argun Akçakanat(The University of Texas MD Anderson Cancer Center), Jithesh J. Augustine(The University of Texas MD Anderson Cancer Center), Huiqin Chen(The University of Texas MD Anderson Cancer Center), Bingbing Dai(The University of Texas MD Anderson Cancer Center), Kurt W. Evans(The University of Texas MD Anderson Cancer Center), Kelly Gale(The University of Texas MD Anderson Cancer Center), Don L. Gibbons(The University of Texas MD Anderson Cancer Center), Min Jin Ha(The University of Texas MD Anderson Cancer Center), V. Behrana Jensen(The University of Texas MD Anderson Cancer Center), Michael P. Kim(The University of Texas MD Anderson Cancer Center), Bryce P. Kirby(The University of Texas MD Anderson Cancer Center), Scott Kopetz(The University of Texas MD Anderson Cancer Center), Christopher D. Lanier(The University of Texas MD Anderson Cancer Center), Dali Li(The University of Texas MD Anderson Cancer Center), Mourad Majidi(The University of Texas MD Anderson Cancer Center), David G. Menter(The University of Texas MD Anderson Cancer Center), Ismail M. Meraz(The University of Texas MD Anderson Cancer Center), Turçin Saridogan(The University of Texas MD Anderson Cancer Center), Stephen Scott(The University of Texas MD Anderson Cancer Center), Alexey V. Sorokin(The University of Texas MD Anderson Cancer Center), Coya Tapia(The University of Texas MD Anderson Cancer Center), Jing Wang(The University of Texas MD Anderson Cancer Center), Shannon N. Westin(The University of Texas MD Anderson Cancer Center), Yuanxin Xi(The University of Texas MD Anderson Cancer Center), Yi Xu(The University of Texas MD Anderson Cancer Center), Fei Yang(The University of Texas MD Anderson Cancer Center), Timothy A. Yap(The University of Texas MD Anderson Cancer Center), Vashisht G. Yennu-Nanda(The University of Texas MD Anderson Cancer Center), Erkan Yuca(The University of Texas MD Anderson Cancer Center), Jianhua Zhang(The University of Texas MD Anderson Cancer Center), Ran Zhang(The University of Texas MD Anderson Cancer Center), Xiaoshan Zhang(The University of Texas MD Anderson Cancer Center), Xiaofeng Zheng(The University of Texas MD Anderson Cancer Center), Dylan Fingerman(The Wistar Institute), Haiyin Lin(The Wistar Institute), Qin Liu(The Wistar Institute), Andrew V. Kossenkov(The Wistar Institute), Vito W. Rebecca(The Wistar Institute), Rajasekharan Somasundaram(The Wistar Institute), Michae T. Tetzlaff(National Cancer Institute), Jayamanna Wickramasinghe(The Wistar Institute), Min Xiao(The Wistar Institute), Xiaowei Xu(National Cancer Institute), Carol J. Bult(Jackson Laboratory), Peter N. Robinson(Jackson Laboratory), Anuj Srivastava(Jackson Laboratory), Michael W. Lloyd(Jackson Laboratory), Steven B. Neuhauser(Jackson Laboratory), Jill C. Rubinstein(Jackson Laboratory), Brian J. Sanderson(Jackson Laboratory), Brian S. White(Jackson Laboratory), Xing Yi Woo(Jackson Laboratory), Tiffany A. Wallace(National Cancer Institute), John D. Minna(Southwestern Medical Center), Boning Gao(Southwestern Medical Center), Luc Girard(Southwestern Medical Center), Hyunsil Park(Southwestern Medical Center), Brenda C. Timmons(Southwestern Medical Center), Katherine L. Nathanson(University of Pennsylvania), George Xu(Hospital of the University of Pennsylvania), Chong-xian Pan(University of California, Davis), Moon S. Chen(University of California, Davis), Luis G. Carvajal‐Carmona(University of California, Davis), May Cho(University of California, Davis), Nicole B. Coggins(University of California, Davis), Ralph W. deVere White(University of California, Davis), Guadalupe Polanco‐Echeverry(University of California, Davis), Ana P. Estrada-Florez(University of California, Davis), David R. Gandara(University of California, Davis), Amanda Kirane(University of California, Davis), Tiffany Le(University of California, Davis), Paul C. Lott(University of California, Davis), Alexa Morales Arana(University of California, Davis), Jonathan W. Reiss(University of California, Davis), Sienna Rocha(University of California, Davis), Clifford G. Tepper(University of California, Davis), Ted Toal(University of California, Davis), Hongyong Zhang(University of California, Davis), Ai‐Hong Ma(University of California, Davis), Brandi N. Davis‐Dusenbery(Seven Bridges Genomics (United States)), Matthew J. Ellis(Baylor College of Medicine), Michael T. Lewis(Baylor College of Medicine), Michael A. Davies(The University of Texas MD Anderson Cancer Center), Meenhard Herlyn(The Wistar Institute), Bingliang Fang(The University of Texas MD Anderson Cancer Center), Jack A. Roth(The University of Texas MD Anderson Cancer Center), Alana L. Welm(University of Utah), Bryan E. Welm(University of Utah), Funda Meric‐Bernstam(The University of Texas MD Anderson Cancer Center), Feng Chen(Washington University in St. Louis), Ryan C. Fields(Washington University in St. Louis), Shunqiang Li(Washington University in St. Louis), Ramaswamy Govindan(Washington University in St. Louis), James H. Doroshow(National Cancer Institute), Jeffrey A. Moscow(National Cancer Institute), Yvonne A. Evrard(Frederick National Laboratory for Cancer Research), Jeffrey H. Chuang(Jackson Laboratory), Benjamin J. Raphael(Princeton University), Li Ding(James S. McDonnell Foundation)
Cited by 108Open Access
Abstract
Development 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 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.