Characterization of HPV and host genome interactions in primary head and neck cancers
Authors: Parfenov Michael , Pedamallu Chandra Sekhar , Gehlenborg Nils , Freeman Samuel S. , Danilova Ludmila , Bristow Christopher A. , Lee Semin , Hadjipanayis Angela G. , Ivanova Elena V. , Wilkerson Matthew D. , Protopopov Alexei , Yang Lixing , Seth Sahil , Song Xingzhi , Tang Jiabin , Ren Xiaojia , Zhang Jianhua , Pantazi Angeliki , Santoso Netty , Xu Andrew W. , Mahadeshwar Harshad , Wheeler David A. , Haddad Robert I. , Jung Joonil , Ojesina Akinyemi I. , Issaeva Natalia , Yarbrough Wendell G. , Hayes D. Neil , Grandis Jennifer R. , El-Naggar Adel K. , Meyerson Matthew , Park Peter J. , Chin Lynda , Seidman J. G. , Hammerman Peter S. , Kucherlapati Raju ,   the Cancer Genome Atlas Network, Ally Adrian , Balasundaram Miruna , Birol Inanc , Bowlby Reanne , Butterfield Yaron S.N. , Carlsen Rebecca , Cheng Dean , Chu Andy , Dhalla Noreen , Guin Ranabir , Holt Robert A. , Jones Steven J.M. , Lee Darlene , Li Haiyan I. , Marra Marco A. , Mayo Michael , Moore Richard A. , Mungall Andrew J. , Robertson A. Gordon , Schein Jacqueline E. , Sipahimalani Payal , Tam Angela , Thiessen Nina , Wong Tina , Protopopov Alexei , Santoso Netty , Lee Semin , Parfenov Michael , Zhang Jianhua , Mahadeshwar Harshad S. , Tang Jiabin , Ren Xiaojia , Seth Sahil , Haseley Psalm , Zeng Dong , Yang Lixing , Xu Andrew W. , Song Xingzhi , Pantazi Angeliki , Bristow Christopher , Hadjipanayis Angela , Seidman Jonathan , Chin Lynda , Park Peter J. , Kucherlapati Raju , Akbani Rehan , Casasent Tod , Liu Wenbin , Lu Yiling , Mills Gordon , Motter Thomas , Weinstein John , Diao Lixia , Wang Jing , Fan You Hong , Liu Jinze , Wang Kai , Auman J. Todd , Balu Saianand , Bodenheimer Tom , Buda Elizabeth , Hayes D. Neil , Hoadley Katherine A. , Hoyle Alan P. , Jefferys Stuart R. , Jones Corbin D. , Kimes Patrick K. , Marron J.S. , Meng Shaowu , Mieczkowski Piotr A. , Mose Lisle E. , Parker Joel S. , Perou Charles M. , Prins Jan F. , Roach Jeffrey , Shi Yan , Simons Janae V. , Singh Darshan , Soloway Mathew G. , Tan Donghui , Veluvolu Umadevi , Walter Vonn , Waring Scot , Wilkerson Matthew D. , Wu Junyuan , Zhao Ni , Cherniack Andrew D. , Hammerman Peter S. , Tward Aaron D. , Pedamallu Chandra Sekhar , Saksena Gordon , Jung Joonil , Ojesina Akinyemi I. , Carter Scott L. , Zack Travis I. , Schumacher Steven E. , Beroukhim Rameen , Freeman Samuel S. , Meyerson Matthew , Cho Juok , Chin Lynda , Getz Gad , Noble Michael S. , DiCara Daniel , Zhang Hailei , Heiman David I. , Gehlenborg Nils , Voet Doug , Lin Pei , Frazer Scott , Stojanov Petar , Liu Yingchun , Zou Lihua , Kim Jaegil , Lawrence Michael S. , Sougnez Carrie , Lichtenstein Lee , Cibulskis Kristian , Lander Eric , Gabriel Stacey B. , Muzny Donna , Doddapaneni HarshaVardhan , Kovar Christie , Reid Jeff , Morton Donna , Han Yi , Hale Walker , Chao Hsu , Chang Kyle , Drummond Jennifer A. , Gibbs Richard A. , Kakkar Nipun , Wheeler David , Xi Liu , Ciriello Giovanni , Ladanyi Marc , Lee William , Ramirez Ricardo , Sander Chris , Shen Ronglai , Sinha Rileen , Weinhold Nils , Taylor Barry S. , Aksoy B. Arman , Dresdner Gideon , Gao Jianjiong , Gross Benjamin , Jacobsen Anders , Reva Boris , Schultz Nikolaus , Sumer S. Onur , Sun Yichao , Chan Timothy , Morris Luc , Stuart Joshua , Benz Stephen , Ng Sam , Benz Christopher , Yau Christina , Baylin Stephen B. , Cope Leslie , Danilova Ludmila , Herman James G. , Bootwalla Moiz , Maglinte Dennis T. , Laird Peter W. , Triche Timothy , Weisenberger Daniel J. , Van Den Berg David J. , Agrawal Nishant , Bishop Justin , Boutros Paul C. , Bruce Jeff P , Byers Lauren Averett , Califano Joseph , Carey Thomas E. , Chen Zhong , Cheng Hui , Chiosea Simion I. , Cohen Ezra , Diergaarde Brenda , Egloff Ann Marie , El-Naggar Adel K. , Ferris Robert L. , Frederick Mitchell J. , Grandis Jennifer R. , Guo Yan , Haddad Robert I. , Hammerman Peter S. , Harris Thomas , Hayes D. Neil , Hui Angela BY , Lee J. Jack , Lippman Scott M. , Liu Fei-Fei , McHugh Jonathan B. , Myers Jeff , Ng Patrick Kwok Shing , Perez-Ordonez Bayardo , Pickering Curtis R. , Prystowsky Michael , Romkes Marjorie , Saleh Anthony D. , Sartor Maureen A. , Seethala Raja , Seiwert Tanguy Y. , Si Han , Tward Aaron D. , Van Waes Carter , Waggott Daryl M. , Wiznerowicz Maciej , Yarbrough Wendell , Zhang Jiexin , Zuo Zhixiang , Burnett Ken , Crain Daniel , Gardner Johanna , Lau Kevin , Mallery David , Morris Scott , Paulauskis Joseph , Penny Robert , Shelton Candance , Shelton Troy , Sherman Mark , Yena Peggy , Black Aaron D. , Bowen Jay , Frick Jessica , Gastier-Foster Julie M. , Harper Hollie A. , Lichtenberg Tara M. , Ramirez Nilsa C. , Wise Lisa , Zmuda Erik , Baboud Julien , Jensen Mark A. , Kahn Ari B. , Pihl Todd D. , Pot David A. , Srinivasan Deepak , Walton Jessica S. , Wan Yunhu , Burton Robert , Davidsen Tanja , Demchok John A. , Eley Greg , Ferguson Martin L. , Shaw Kenna R. Mills , Ozenberger Bradley A. , Sheth Margi , Sofia Heidi J. , Tarnuzzer Roy , Wang Zhining , Yang Liming , Zenklusen Jean Claude , Saller Charles , Tarvin Katherine , Chen Chu , Bollag Roni , Weinberger Paul , Golusiński Wojciech , Golusiński Paweł , Ibbs Matthiew , Korski Konstanty , Mackiewicz Andrzej , Suchorska Wiktoria , Szybiak Bartosz , Wiznerowicz Maciej , Burnett Ken , Curley Erin , Gardner Johanna , Mallery David , Penny Robert , Shelton Troy , Yena Peggy , Beard Christina , Mitchell Colleen , Sandusky George , Agrawal Nishant , Ahn Julie , Bishop Justin , Califano Joseph , Khan Zubair , Bruce Jeff P , Hui Angela BY , Irish Jonathan , Liu Fei-Fei , Perez-Ordonez Bayardo , Waldron John , Boutros Paul C. , Waggott Daryl M. , Myers Jeff , Lippman Scott M. , Egea Sophie , Gomez-Fernandez Carmen , Herbert Lynn , Bradford Carol R. , Carey Thomas E. , Chepeha Douglas B. , Haddad Andrea S. , Jones Tamara R. , Komarck Christine M. , Malakh Mayya , McHugh Jonathan B. , Moyer Jeffrey S. , Nguyen Ariane , Peterson Lisa A. , Prince Mark E. , Rozek Laura S. , Sartor Maureen A. , Taylor Evan G. , Walline Heather M. , Wolf Gregory T. , Boice Lori , Chera Bhishamjit S. , Funkhouser William K. , Gulley Margaret L. , Hackman Trevor G. , Hayes D. Neil , Hayward Michele C. , Huang Mei , Rathmell W. Kimryn , Salazar Ashley H. , Shockley William W. , Shores Carol G. , Thorne Leigh , Weissler Mark C. , Wrenn Sylvia , Zanation Adam M. , Chiosea Simion I. , Diergaarde Brenda , Egloff Ann Marie , Ferris Robert L. , Romkes Marjorie , Seethala Raja , Brown Brandee T. , Guo Yan , Pham Michelle , Yarbrough Wendell G. 
Published: October 2014

Significance

A significant proportion of head and neck cancer is driven by human papillomavirus (HPV) infection, and the expression of viral oncogenes is involved in the development of these tumors. However, the role of HPV integration in primary tumors beyond increasing the expression of viral oncoproteins is not understood. Here, we describe how HPV integration impacts the host genome by amplification of oncogenes and disruption of tumor suppressors as well as driving inter- and intrachromosomal rearrangements. Tumors that do and do not have HPV integrants display distinct gene expression profiles and DNA methylation patterns, which further support the view that the mechanisms by which tumors with integrated and nonintegrated HPV arise are distinct.