| Literature DB >> 26760213 |
A Sorana Morrissy1,2, Livia Garzia1,2, David J H Shih1,2,3, Scott Zuyderduyn4, Xi Huang1, Patryk Skowron1,2,3, Marc Remke5, Florence M G Cavalli1,2, Vijay Ramaswamy1,2,3,6, Patricia E Lindsay7,8, Salomeh Jelveh8, Laura K Donovan1,2, Xin Wang1,2,3, Betty Luu1,2, Kory Zayne1,2, Yisu Li9, Chelsea Mayoh9, Nina Thiessen9, Eloi Mercier9, Karen L Mungall9, Yusanne Ma9, Kane Tse9, Thomas Zeng9, Karey Shumansky10, Andrew J L Roth10, Sohrab Shah10, Hamza Farooq1,2, Noriyuki Kijima1,2, Borja L Holgado1,2, John J Y Lee1,2,3, Stuart Matan-Lithwick1,2, Jessica Liu1,2, Stephen C Mack1,2,11, Alex Manno1,2, K A Michealraj1,2, Carolina Nor1,2, John Peacock1,2,3, Lei Qin1,2, Juri Reimand2,4, Adi Rolider1,2, Yuan Y Thompson1,2,3, Xiaochong Wu1,2, Trevor Pugh12, Adrian Ally9, Mikhail Bilenky9, Yaron S N Butterfield9, Rebecca Carlsen9, Young Cheng9, Eric Chuah9, Richard D Corbett9, Noreen Dhalla9, An He9, Darlene Lee9, Haiyan I Li9, William Long9, Michael Mayo9, Patrick Plettner9, Jenny Q Qian9, Jacqueline E Schein9, Angela Tam9, Tina Wong9, Inanc Birol9,13,14, Yongjun Zhao9, Claudia C Faria15, José Pimentel16, Sofia Nunes17, Tarek Shalaby18, Michael Grotzer18, Ian F Pollack19, Ronald L Hamilton20, Xiao-Nan Li21, Anne E Bendel22, Daniel W Fults23, Andrew W Walter24, Toshihiro Kumabe25, Teiji Tominaga26, V Peter Collins27, Yoon-Jae Cho28, Caitlin Hoffman6, David Lyden29, Jeffrey H Wisoff30, James H Garvin31, Duncan S Stearns32, Luca Massimi33, Ulrich Schüller34, Jaroslav Sterba35, Karel Zitterbart35, Stephanie Puget36, Olivier Ayrault37, Sandra E Dunn38, Daniela P C Tirapelli39, Carlos G Carlotti39, Helen Wheeler40, Andrew R Hallahan41,42, Wendy Ingram41,43, Tobey J MacDonald44, Jeffrey J Olson45, Erwin G Van Meir46, Ji-Yeoun Lee47, Kyu-Chang Wang47, Seung-Ki Kim47, Byung-Kyu Cho47, Torsten Pietsch48, Gudrun Fleischhack49, Stephan Tippelt49, Young Shin Ra50, Simon Bailey51, Janet C Lindsey51, Steven C Clifford51, Charles G Eberhart52, Michael K Cooper53, Roger J Packer54, Maura Massimino55, Maria Luisa Garre56, Ute Bartels57, Uri Tabori2,57, Cynthia E Hawkins2,58, Peter Dirks2,6, Eric Bouffet2,57, James T Rutka2,3,6, Robert J Wechsler-Reya59, William A Weiss60, Lara S Collier61, Adam J Dupuy62, Andrey Korshunov63, David T W Jones64, Marcel Kool64, Paul A Northcott64, Stefan M Pfister64,65, David A Largaespada66, Andrew J Mungall9, Richard A Moore9, Nada Jabado67, Gary D Bader4,68, Steven J M Jones9,13,69, David Malkin57,70, Marco A Marra9,13, Michael D Taylor1,2,3,6.
Abstract
The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.Entities:
Mesh：
Year: 2016 PMID： 26760213 PMCID： PMC4936195 DOI： 10.1038/nature16478
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962