| Literature DB >> 27960086 |
Jonathon Torchia1, Brian Golbourn2, Shengrui Feng3, King Ching Ho4, Patrick Sin-Chan1, Alexandre Vasiljevic5, Joseph D Norman4, Paul Guilhamon6, Livia Garzia7, Natalia R Agamez4, Mei Lu4, Tiffany S Chan1, Daniel Picard4, Pasqualino de Antonellis7, Dong-Anh Khuong-Quang8, Aline C Planello6, Constanze Zeller6, Dalia Barsyte-Lovejoy6, Lucie Lafay-Cousin9, Louis Letourneau10, Mathieu Bourgey10, Man Yu11, Deena M A Gendoo4, Misko Dzamba12, Mark Barszczyk11, Tiago Medina6, Alexandra N Riemenschneider13, A Sorana Morrissy7, Young-Shin Ra14, Vijay Ramaswamy4, Marc Remke4, Christopher P Dunham15, Stephen Yip16, Ho-Keung Ng17, Jian-Qiang Lu18, Vivek Mehta19, Steffen Albrecht20, Jose Pimentel21, Jennifer A Chan22, Gino R Somers23, Claudia C Faria24, Lucia Roque25, Maryam Fouladi26, Lindsey M Hoffman27, Andrew S Moore28, Yin Wang29, Seung Ah Choi30, Jordan R Hansford31, Daniel Catchpoole32, Diane K Birks27, Nicholas K Foreman27, Doug Strother33, Almos Klekner34, Laszló Bognár34, Miklós Garami35, Péter Hauser35, Tibor Hortobágyi36, Beverly Wilson33, Juliette Hukin37, Anne-Sophie Carret38, Timothy E Van Meter39, Eugene I Hwang40, Amar Gajjar41, Shih-Hwa Chiou42, Hideo Nakamura43, Helen Toledano44, Iris Fried45, Daniel Fults46, Takafumi Wataya47, Chris Fryer37, David D Eisenstat33, Katrin Scheinemann48, Adam J Fleming48, Donna L Johnston49, Jean Michaud50, Shayna Zelcer51, Robert Hammond52, Samina Afzal53, David A Ramsay52, Nongnuch Sirachainan54, Suradej Hongeng54, Noppadol Larbcharoensub55, Richard G Grundy56, Rishi R Lulla57, Jason R Fangusaro57, Harriet Druker58, Ute Bartels58, Ronald Grant58, David Malkin59, C Jane McGlade60, Theodore Nicolaides61, Tarik Tihan62, Joanna Phillips62, Jacek Majewski63, Alexandre Montpetit10, Guillaume Bourque63, Gary D Bader64, Alyssa T Reddy65, G Yancey Gillespie66, Monika Warmuth-Metz67, Stefan Rutkowski68, Uri Tabori69, Mathieu Lupien3, Michael Brudno70, Ulrich Schüller71, Torsten Pietsch72, Alexander R Judkins73, Cynthia E Hawkins74, Eric Bouffet4, Seung-Ki Kim30, Peter B Dirks13, Michael D Taylor75, Anat Erdreich-Epstein76, Cheryl H Arrowsmith6, Daniel D De Carvalho77, James T Rutka78, Nada Jabado79, Annie Huang80.
Abstract
We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.Entities:
Keywords: ATRT; enhancer; epigenomics; genomics; rhabdoid tumors; subgroup-specific therapeutics
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Year: 2016 PMID： 27960086 PMCID： PMC5500911 DOI： 10.1016/j.ccell.2016.11.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743