Characterization of HPV and host genome interactions in primary head and neck cancers

著者: Michael Parfenov, Chandra Sekhar Pedamallu, Nils Gehlenborg, Samuel S. Freeman, Ludmila Danilova, Christopher A. Bristow, Semin Lee, Angela Hadjipanayis, Elena V. Ivanova, Matthew D. Wilkerson, Alexei Protopopov, Lixing Yang, Sahil Seth, Xingzhi Song, Jiabin Tang, Xiaojia Ren, Jianhua Zhang, Angeliki Pantazi, Netty Santoso, Andrew W. Xu, Harshad S. Mahadeshwar, David A. Wheeler, Robert I. Haddad, Joonil Jung, Akinyemi I. Ojesina, Natalia Issaeva, Wendell G. Yarbrough, D. Neil Hayes, Jennifer R. Grandis, Adel K. El‐Naggar, Matthew Meyerson, Peter J. Park, Lynda Chin, Jonathan G. Seidman, Peter S. Hammerman, Raju Kucherlapati, 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, 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 W. 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 Motter, John N. Weinstein, Lixia Diao, Jing Wang, You Hong Fan, Jinze Liu, Kai Wang, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Elizabeth Buda, D. Neil Hayes, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Patrick K. Kimes, J. S. Marron, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Peter J. Park, Charles M. Perou, Jan F. Prins, Jeffrey Roach, Yan Shi, Janae V. Simons, Darshan Singh, Mathew 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 Zack, Steven E. Schumacher, Rameen Beroukhim, Samuel S. Freeman, Matthew Meyerson, Juok Cho, Lynda Chin, Gad Getz, 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, Michael S. Lawrence, Carrie Sougnez, Lee Lichtenstein, Kristian Cibulskis, Eric Lander, Stacey Gabriel, Donna M. Muzny, HarshaVardhan Doddapaneni, Christie Kovar, Jeff G. Reid, Donna Morton, Yi Han, Walker Hale, Hsu Chao, Kyle Chang, Jennifer Drummond, Richard A. Gibbs, Nipun Kakkar, David A. Wheeler, Xi Liu, Giovanni Ciriello, Marc Ladanyi, William Lee, Ricardo J. Ramirez, Chris Sander, Ronglai Shen, Rileen Sinha, 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, Timothy En Haw 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 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, Adel K. El‐Naggar, Robert L. Ferris, Mitchell J. Frederick, Jennifer R. Grandis, Yan Guo, Robert I. Haddad, Peter S. Hammerman, Thomas M. Harris, D. Neil Hayes, Angela BY Hui, J. Jack Lee, Scott M. Lippman, Fei-Fei Liu, Jonathan B. McHugh, Jeff Myers, Patrick Kwok Shing Ng, Bayardo Perez‐Ordoñez, Curtis R. Pickering, Michael B. Prystowsky, Marjorie Romkes, Anthony D. Saleh, Maureen A. Sartor, Raja R. Seethala, Tanguy Y. Seiwert, Han Si, Aaron D. Tward, 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, 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, David Pot, Deepak Srinivasan, Jessica S. Walton, Yunhu Wan, Robert Burton, Tanja M. 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 Weinberger, Wojciech Golusiński, Paweł Golusiński, Matthiew Ibbs, Konstanty Korski, Andrzej Maćkiewicz, Wiktoria Maria Suchorska, Bartosz Szybiak, Maciej Wiznerowicz, Ken Burnett, Erin Curley, Johanna Gardner, David Mallery, 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, 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, Gregory T. Wolf, Lori Boice, Bhishamjit S. Chera, William K. Funkhouser, Margaret L. Gulley, Trevor Hackman, D. Neil Hayes, 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, Yan Guo, Michelle Pham, Wendell G. Yarbrough - Proceedings of the National Academy of Sciences, PNAS 2014 被引用: 395

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.