Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation
Luc G. T. Morris,Andrew Kaufman,Yongxing Gong,Deepa Ramaswami,Logan A. Walsh,Sevin Turcan,Stephanie Eng,Kasthuri Kannan,Yilong Zou,Luke Peng,Victoria E. Banuchi,P. Paty,Zhaoshi Zeng,Efsevia Vakiani,David B. Solit,Bhuvanesh Singh,Ian Ganly,Linda M. Liau,Timothy C. Cloughesy,Paul S. Mischel,Ingo K. Mellinghoff,Timothy A. Chan +21 more
TLDR
Recurrent somatic mutations of the Drosophila melanogaster tumor suppressor–related gene FAT1 in glioblastoma, colorectal cancer, and head and neck cancer strongly point to FAT1 as a tumor suppressing gene driving loss of chromosome 4q35, a prevalent region of deletion in cancer.Abstract:
Aberrant Wnt signaling can drive cancer development. In many cancer types, the genetic basis of Wnt pathway activation remains incompletely understood. Here, we report recurrent somatic mutations of the Drosophila melanogaster tumor suppressor-related gene FAT1 in glioblastoma (20.5%), colorectal cancer (7.7%), and head and neck cancer (6.7%). FAT1 encodes a cadherin-like protein, which we found is able to potently suppress cancer cell growth in vitro and in vivo by binding β-catenin and antagonizing its nuclear localization. Inactivation of FAT1 via mutation therefore promotes Wnt signaling and tumorigenesis and affects patient survival. Taken together, these data strongly point to FAT1 as a tumor suppressor gene driving loss of chromosome 4q35, a prevalent region of deletion in cancer. Loss of FAT1 function is a frequent event during oncogenesis. These findings address two outstanding issues in cancer biology: the basis of Wnt activation in non-colorectal tumors and the identity of a 4q35 tumor suppressor.read more
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Comprehensive genomic characterization of head and neck squamous cell carcinomas
Michael S. Lawrence,Carrie Sougnez,Lee Lichtenstein,Kristian Cibulskis,Eric S. Lander,Stacey Gabriel,Gad Getz,Adrian Ally,Miruna Balasundaram,Inanc Birol,Reanne Bowlby,Denise Brooks,Yaron S.N. Butterfield,Rebecca Carlsen,Dean Cheng,Andy Chu,Noreen Dhalla,Ranabir Guin,Robert A. Holt,Steven J.M. Jones,Darlene Lee,Haiyan I. Li,Marco A. Marra,Michael Mayo,Richard A. Moore,Andrew J. Mungall,A. Gordon Robertson,Jacqueline E. Schein,Payal Sipahimalani,Angela Tam,Nina Thiessen,Tina Wong,Alexei Protopopov,Netty Santoso,Semin Lee,Michael Parfenov,Jianhua Zhang,Harshad S. Mahadeshwar,Jiabin Tang,Xiaojia Ren,Sahil Seth,Psalm Haseley,Dong Zeng,Lixing Yang,Andrew Wei Xu,Xingzhi Song,Angeliki Pantazi,Christopher A. Bristow,Angela Hadjipanayis,Jonathan G. Seidman,Lynda Chin,Peter J. Park,Raju Kucherlapati,Rehan Akbani,Tod D. Casasent,Wenbin Liu,Yiling Lu,Gordon B. Mills,Thomas C. Motter,John N. Weinstein,Lixia Diao,Jing Wang,You Hong Fan,Jinze Liu,Kai Wang,J. Todd Auman,Saianand Balu,Thomas Bodenheimer,Elizabeth Buda,D. Neil Hayes,Katherine A. Hoadley,Alan P. Hoyle,Stuart R. Jefferys,Corbin D. Jones,Patrick K. Kimes,Yufeng Liu,James Stephen Marron,Shaowu Meng,Piotr A. Mieczkowski,Lisle E. Mose,Joel S. Parker,Charles M. Perou,Jan F. Prins,Jeffrey Roach,Yan Shi,Janae V. Simons,Darshan Singh,Matthew G. Soloway,Donghui Tan,Umadevi Veluvolu,Vonn Walter,Scot Waring,Matthew D. Wilkerson,Junyuan Wu,Ni Zhao,Andrew D. Cherniack,Peter S. Hammerman,Aaron D. Tward,Chandra Sekhar Pedamallu,Gordon Saksena,Joonil Jung,Akinyemi I. Ojesina,Scott L. Carter,Travis I. Zack,Steven E. Schumacher,Rameen Beroukhim,Samuel S. Freeman,Matthew Meyerson,Juok Cho,Michael S. Noble,Daniel DiCara,Hailei Zhang,David I. Heiman,Nils Gehlenborg,Doug Voet,Pei Lin,Scott Frazer,Petar Stojanov,Yingchun Liu,Lihua Zou,Jaegil Kim,Donna M. Muzny,Harshavardhan Doddapaneni,Christie Kovar,Jeffrey S. Reid,Donna Morton,Yi Han,Walker Hale,Hsu Chao,Kyle Chang,Jennifer Drummond,Richard A. Gibbs,Nipun Kakkar,David A. Wheeler,Liu Xi,Giovanni Ciriello,Marc Ladanyi,William Lee,Ricardo Ramirez,Chris Sander,Ronglai Shen,Rileen Sinha,Nils Weinhold,Barry S. Taylor,B. Arman Aksoy,Gideon Dresdner,Jianjiong Gao,Benjamin Gross,Anders Jacobsen,Boris Reva,Nikolaus Schultz,S. Onur Sumer,Yichao Sun,Timothy A. Chan,Luc G. T. Morris,Joshua M. Stuart,Stephen C. Benz,Sam Ng,Christopher C. Benz,Christina Yau,Stephen B. Baylin,Leslie Cope,Ludmila Danilova,James G. Herman,Moiz S. Bootwalla,Dennis T. Maglinte,Peter W. Laird,Timothy J. Triche,Daniel J. Weisenberger,David Van Den Berg,Nishant Agrawal,Justin A. Bishop,Paul C. Boutros,Jeff Bruce,Lauren Averett Byers,Joseph A. Califano,Thomas E. Carey,Zhong Chen,Hui Cheng,Simion I. Chiosea,Ezra E.W. Cohen,Brenda Diergaarde,Ann Marie Egloff,Adel K. El-Naggar,Robert L. Ferris,Mitchell J. Frederick,Jennifer R. Grandis,Yan Guo,Robert I. Haddad,Thomas M. Harris,Angela B.Y. Hui,J. Jack Lee,Scott M. Lippman,Fei-Fei Liu,Jonathan B. McHugh,Jeffrey N. Myers,Patrick Kwok Shing Ng,Bayardo Perez-Ordonez,Curtis R. Pickering,Michael B. Prystowsky,Marjorie Romkes,Anthony Saleh,Maureen A. Sartor,Raja R. Seethala,Tanguy Y. Seiwert,Han Si,Carter Van Waes,Daryl Waggott,Maciej Wiznerowicz,Wendell G. Yarbrough,Jiexin Zhang,Zhixiang Zuo,Ken Burnett,Daniel Crain,Johanna Gardner,Kevin Lau,David Mallery,Scott Morris,Joseph Paulauskis,Robert Penny,Candace Shelton,Troy Shelton,Mark E. Sherman,Peggy Yena,Aaron D. Black,Jay Bowen,Jessica Frick,Julie M. Gastier-Foster,Hollie A. Harper,Kristen M. Leraas,Tara M. Lichtenberg,Nilsa C. Ramirez,Lisa Wise,Erik Zmuda,Julien Baboud,Mark A. Jensen,Ari B. Kahn,Todd Pihl,David Pot,Deepak Srinivasan,Jessica Walton,Yunhu Wan,Robert A. Burton,Tanja Davidsen,John A. Demchok,Greg Eley,Martin L. Ferguson,Kenna R. Mills Shaw,Bradley A. Ozenberger,Margi Sheth,Heidi J. Sofia,Roy Tarnuzzer,Zhining Wang,Liming Yang,Jean C. Zenklusen,Charles Saller,Katherine Tarvin,Chu Chen,Roni J. Bollag,Paul M. Weinberger,Wojciech Golusiński,Paweł Golusiński,Matthew Ibbs,Konstanty Korski,Andrzej Mackiewicz,Wiktoria Maria Suchorska,Bartosz Szybiak,Erin Curley,Christina Beard,Colleen Mitchell,George E. Sandusky,Julie Ahn,Zubair Khan,Jonathan C. Irish,John Waldron,William N. William,Sophie C. Egea,Carmen Gomez-Fernandez,Lynn M. Herbert,Carol R. Bradford,Douglas B. Chepeha,Andrea Haddad,Tamara R. Jones,Christine M. Komarck,Mayya Malakh,Jeffrey S. Moyer,Ariane Nguyen,Lisa A. Peterson,Mark E. Prince,Laura S. Rozek,Evan G. Taylor,Heather M. Walline,Gregory T. Wolf,Lori Boice,Bhishamjit S. Chera,William K. Funkhouser,Margaret L. Gulley,Trevor Hackman,Michele C. Hayward,Mei Huang,W. Kimryn Rathmell,Ashley H. Salazar,William W. Shockley,Carol G. Shores,Leigh B. Thorne,Mark C. Weissler,Sylvia Wrenn,Adam M. Zanation,Brandee T. Brown,Michelle Q. Pham +309 more
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