Characterization of HPV and host genome interactions in primary head and neck cancers
Michael Parfenov(Emory University), Chandra Sekhar Pedamallu(Broad Institute), Nils Gehlenborg(Broad Institute), Samuel S. Freeman(Broad Institute), Ludmila Danilova(Johns Hopkins University), Christopher A. Bristow(The University of Texas MD Anderson Cancer Center), Semin Lee(Harvard University), Angela Hadjipanayis(Emory University), Elena V. Ivanova(Harvard University Press), Matthew D. Wilkerson(University of North Carolina at Chapel Hill), Alexei Protopopov(The University of Texas MD Anderson Cancer Center), Lixing Yang(Harvard University), Sahil Seth(The University of Texas MD Anderson Cancer Center), Xingzhi Song(The University of Texas MD Anderson Cancer Center), Jiabin Tang(The University of Texas MD Anderson Cancer Center), Xiaojia Ren(Emory University), Jianhua Zhang(The University of Texas MD Anderson Cancer Center), Angeliki Pantazi(Emory University), Netty Santoso(Emory University), Andrew W. Xu(Harvard University), Harshad S. Mahadeshwar(The University of Texas MD Anderson Cancer Center), David A. Wheeler(Baylor College of Medicine), Robert I. Haddad(Harvard University Press), Joonil Jung(Broad Institute), Akinyemi I. Ojesina(Broad Institute), Natalia Issaeva(Yale University), Wendell G. Yarbrough(Yale University), D. Neil Hayes(University of North Carolina at Chapel Hill), Jennifer R. Grandis(University of Pittsburgh), Adel K. El‐Naggar(The University of Texas MD Anderson Cancer Center), Matthew Meyerson(Broad Institute), Peter J. Park(Harvard University), Lynda Chin(Broad Institute), Jonathan G. Seidman(Emory University), Peter S. Hammerman(Broad Institute), Raju Kucherlapati(Harvard University), the Cancer Genome Atlas Network, Adrian Ally, Miruna Balasundaram, İnanç Birol, Reanne Bowlby, Yaron S.N. Butterfield, Rebecca Carlsen, Dean Cheng, Andy Chu, Noreen Dhalla, Ranabir Guin(Dana-Farber Cancer Institute), Robert A. Holt, Steven J.M. Jones(Harvard University), Darlene Lee(University of Pittsburgh), Haiyan I. Li, Marco A. Marra(Emory University), Michael Mayo, Richard A. Moore, Andrew J. Mungall, A. Gordon Robertson, Jacqueline E. Schein, Payal Sipahimalani(Emory University), Angela Tam, Nina Thiessen, Tina Wong(The University of Texas MD Anderson Cancer Center), Alexei Protopopov(Emory University), Netty Santoso(Harvard University Press), Semin Lee(Harvard University), Michael Parfenov(The University of Texas MD Anderson Cancer Center), Jianhua Zhang(The University of Texas MD Anderson Cancer Center), Harshad S. Mahadeshwar(The University of Texas MD Anderson Cancer Center), Jiabin Tang(Emory University), Xiaojia Ren(The University of Texas MD Anderson Cancer Center), Sahil Seth(Institute for Applied Science), Psalm Haseley, Dong Zeng(Harvard University Press), Lixing Yang(Harvard University), Andrew W. Xu(The University of Texas MD Anderson Cancer Center), Xingzhi Song(Emory University), Angeliki Pantazi(The University of Texas MD Anderson Cancer Center), Christopher A. Bristow(Harvard University Press), Angela Hadjipanayis(Harvard University Press), Jonathan G. Seidman(Massachusetts Institute of Technology), Lynda Chin(Broad Institute), Peter J. Park(Harvard University), Raju Kucherlapati(Harvard University), Rehan Akbani, Tod D. Casasent, Wenbin Liu(Johns Hopkins University), Yiling Lu, Gordon B. Mills, Thomas Motter, John N. Weinstein, Lixia Diao, Jing Wang, You Hong Fan, Jinze Liu, Kai Wang, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Elizabeth Buda(University of North Carolina at Chapel Hill), D. Neil Hayes(University of North Carolina at Chapel Hill), Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Patrick K. Kimes(Emory University), J. S. Marron, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Peter J. Park, Charles M. Perou, Jan F. Prins, Jeffrey Roach(Harvard University), Yan Shi, Janae V. Simons, Darshan Singh, Mathew G. Soloway(The University of Texas MD Anderson Cancer Center), Donghui Tan, Umadevi Veluvolu, Vonn Walter, Scot Waring(University of North Carolina at Chapel Hill), Matthew D. Wilkerson(UNC Lineberger Comprehensive Cancer Center), Junyuan Wu(Emory University), Ni Zhao, Andrew D. Cherniack(Massachusetts Institute of Technology), Peter S. Hammerman(Broad Institute), Aaron D. Tward(Massachusetts Institute of Technology), Chandra Sekhar Pedamallu(Broad Institute), Gordon Saksena(Massachusetts Institute of Technology), Joonil Jung(Broad Institute), Akinyemi I. Ojesina(Broad Institute), Scott L. Carter, Travis Zack, Steven E. Schumacher, Rameen Beroukhim(Massachusetts Institute of Technology), Samuel S. Freeman(Broad Institute), Matthew Meyerson(Broad Institute), Juok Cho(Massachusetts Institute of Technology), Lynda Chin(Broad Institute), Gad Getz, Michael S. Noble, Daniel DiCara(The University of Texas MD Anderson Cancer Center), Hailei Zhang, David I. Heiman(Harvard University Press), Nils Gehlenborg(Broad Institute), Doug Voet, Pei Lin, Scott Frazer, Petar Stojanov, Yingchun Liu, Lihua Zou, Jaegil Kim, Michael S. Lawrence, Carrie Sougnez(Harvard University), Lee Lichtenstein, Kristian Cibulskis, Eric Lander, Stacey Gabriel, Donna M. Muzny, HarshaVardhan Doddapaneni, Christie Kovar, Jeff G. Reid, Donna Morton(The University of Texas MD Anderson Cancer Center), Yi Han, Walker Hale, Hsu Chao, Kyle Chang(Emory University), Jennifer Drummond, Richard A. Gibbs, Nipun Kakkar(Baylor College of Medicine), David A. Wheeler(Emory University), Xi Liu, Giovanni Ciriello, Marc Ladanyi(Harvard University), William Lee, Ricardo J. Ramirez(The University of Texas MD Anderson Cancer Center), Chris Sander, Ronglai Shen, Rileen Sinha(Broad Institute), Nils Weinhold, Barry S. Taylor, Bülent Arman Aksoy, Gideon Dresdner, Jianjiong Gao, Benjamin E. Gross, Anders Jacobsen, Boris Reva, Nikolaus Schultz, S. Onur Sumer, Yichao Sun(Broad Institute), Timothy En Haw Chan, Luc G.T. Morris, Joshua M. Stuart, Stephen C. Benz(Broad Institute), Sam Ng(The University of Texas MD Anderson Cancer Center), Christopher C. Benz, Christina Yau, Stephen B. Baylin, Leslie Cope(Johns Hopkins University), Ludmila Danilova(Johns Hopkins University), James G. Herman, Moiz 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 P 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(The University of Texas MD Anderson Cancer Center), Adel K. El‐Naggar(The University of Texas MD Anderson Cancer Center), Robert L. Ferris, Mitchell J. Frederick(University of Pittsburgh), Jennifer R. Grandis(Harvard University), Yan Guo(Harvard University Press), Robert I. Haddad(Dana-Farber Cancer Institute), Peter S. Hammerman(Broad Institute), Thomas M. Harris(University of North Carolina at Chapel Hill), D. Neil Hayes(University of North Carolina at Chapel Hill), Angela BY Hui(Harvard University), J. Jack Lee, Scott M. Lippman, Fei-Fei Liu, Jonathan B. McHugh, Jeff Myers(Broad Institute), Patrick Kwok Shing Ng, Bayardo Perez‐Ordoñez, Curtis R. Pickering(Emory University), Michael B. Prystowsky, Marjorie Romkes, Anthony D. Saleh, Maureen A. Sartor, Raja R. Seethala, Tanguy Y. Seiwert(Broad Institute), Han Si, Aaron D. Tward, Carter Van Waes, Daryl Waggott, Maciej Wiznerowicz(Yale University), Wendell G. Yarbrough(The University of Texas MD Anderson Cancer Center), Jiexin Zhang(Institute for Applied Science), Zhixiang Zuo, Ken Burnett, Daniel Crain, Johanna Gardner, Kevin Lau(Baylor College of Medicine), David Mallery, Scott Morris, Joseph Paulauskis(Dana-Farber Cancer Institute), Robert Penny, Candance Shelton, Troy Shelton, Mark E. Sherman, Peggy Yena, Aaron D. Black, Jay Bowen, Jessica Frick, Julie M. Gastier‐Foster, Hollie A. Harper, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Julien Baboud, Mark A. Jensen, A Kahn, Todd Pihl(Baylor College of Medicine), David Pot, Deepak Srinivasan, Jessica S. Walton, Yunhu Wan(Dana-Farber Cancer Institute), Robert Burton, Tanja M. Davidsen, John A. Demchok(Emory University), Greg Eley, Martin L. Ferguson, Kenna R. Mills Shaw, Bradley A. Ozenberger, Margi Sheth, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang(Harvard University Press), Liming Yang(Harvard University), Jean C. Zenklusen, Charles Saller, Katherine Tarvin, Chu Chen, Roni J. Bollag, Paul Weinberger, Wojciech Golusiński, Paweł Golusiński, Matthiew Ibbs, Konstanty Korski, Andrzej Maćkiewicz, Wiktoria Maria Suchorska, Bartosz Szybiak, Maciej Wiznerowicz, Ken Burnett, Erin Curley, Johanna Gardner(Baylor College of Medicine), David Mallery(Dana-Farber Cancer Institute), Robert Penny, Troy Shelton, Peggy Yena, Christina Beard, Colleen M. Mitchell, George E. Sandusky, Nishant Agrawal, Julie Ahn, Justin Bishop, Joseph A. Califano, Zubair Khan, Jeff P Bruce, Angela BY Hui, Jonathan Irish, Fei-Fei Liu, Bayardo Perez‐Ordoñez, John Waldron, Paul C. Boutros, Daryl Waggott, Jeff Myers, Scott M. Lippman, Sophie Egea, Carmen Gomez‐Fernandez, Lynn M. Herbert, Carol R. Bradford, Thomas E. Carey, Douglas B. Chepeha(Dana-Farber Cancer Institute), Andrea S. Haddad, Tamara R. Jones, Christine M. Komarck, Mayya Malakh, Jonathan B. McHugh, Jeffrey S. Moyer, Ariane Nguyen, Lisa A. Peterson, Mark E. Prince, Laura S. Rozek, Maureen A. Sartor, Evan G. Taylor, Heather M. Walline(Emory University), Gregory T. Wolf, Lori Boice, Bhishamjit S. Chera, William K. Funkhouser, Margaret L. Gulley, Trevor Hackman(University of North Carolina at Chapel Hill), D. Neil Hayes(University of North Carolina at Chapel Hill), Michele C. Hayward, Mei Huang, W. Kimryn Rathmell, Ashley H. Salazar, W. Shockley, Carol G. Shores, Leigh B. Thorne, Mark C. Weissler, S. Jarrett Wrenn, Adam M. Zanation, Simion I. Chiosea, Brenda Diergaarde, Ann Marie Egloff, Robert L. Ferris, Marjorie Romkes, Raja R. Seethala, Brandee Brown(Harvard University), Yan Guo, Michelle Pham(Yale University), Wendell G. Yarbrough(Yale University)
Cited by 394Open Access
Abstract
Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.
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