Integrated genomic and molecular characterization of cervical cancer.

Citation data:

Nature, ISSN: 1476-4687, Vol: 543, Issue: 7645, Page: 378-384

Publication Year:
2017
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Repository URL:
https://ohsu.pure.elsevier.com/en/publications/25969159-a9ce-489a-918f-d6122ea9829f; http://scholarworks.unist.ac.kr/handle/201301/21228
PMID:
28112728
DOI:
10.1038/nature21386
Author(s):
Robert D. Burk; Zigui Chen; Charles Saller; Katherine Tarvin; Andre L. Carvalho; Cristovam Scapulatempo-Neto; Henrique C. Silveira; José H. Fregnani; Chad J. Creighton; Matthew L. Anderson; Patricia Castro; Sophia S. Wang; Christina Yau; Christopher Benz; A. Gordon Robertson; Karen Mungall; Lynette Lim; Reanne Bowlby; Sara Sadeghi; Denise Brooks; Payal Sipahimalani; Richard Mar; Adrian Ally; Amanda Clarke; Andrew J. Mungall; Angela Tam; Darlene Lee; Eric Chuah; Jacqueline E. Schein; Kane Tse; Katayoon Kasaian; Yussanne Ma; Marco A. Marra; Michael Mayo; Miruna Balasundaram; Nina Thiessen; Noreen Dhalla; Rebecca Carlsen; Richard A. Moore; Robert A. Holt; Steven J.M. Jones; Tina Wong; Angeliki Pantazi; Michael Parfenov; Raju Kucherlapati; Angela Hadjipanayis; Jonathan Seidman; Melanie Kucherlapati; Xiaojia Ren; Andrew W. Xu; Lixing Yang; Peter J. Park; Semin Lee; Brenda Rabeno; Lori Huelsenbeck-Dill; Mark Borowsky; Mark Cadungog; Mary Iacocca; Nicholas Petrelli; Patricia Swanson; Akinyemi I. Ojesina; Bradley A. Murray; Hailei Zhang; Andrew D. Cherniack; Carrie Sougnez; Chandra Sekhar Pedamallu; Lee Lichtenstein; Matthew Meyerson; Michael S. Noble; David I. Heiman; Doug Voet; Gad Getz; Gordon Saksena; Jaegil Kim; Juliann Shih; Juok Cho; Michael S. Lawrence; Nils Gehlenborg; Pei Lin; Rameen Beroukhim; Scott Frazer; Stacey B. Gabriel; Steven E. Schumacher; Xuan Le; George Sandusky; Sally N. Adebamowo; Teniola Akeredolu; Clement Adebamowo; Sheila M. Reynolds; Ilya Shmulevich; Candace Shelton; Daniel Crain; David Mallery; Erin Curley; Johanna Gardner; Robert Penny; Scott Morris; Troy Shelton; Jia Liu; Laxmi Lolla; Sudha Chudamani; Ye Wu; Michael Birrer; Michael D. McLellan; Matthew H. Bailey; Christopher A. Miller; Matthew A. Wyczalkowski; Robert S. Fulton; Catrina C. Fronick; Charles Lu; Elaine R. Mardis; Elizabeth L. Appelbaum; Heather K. Schmidt; Lucinda A. Fulton; Matthew G. Cordes; Tiandao Li; Li Ding; Richard K. Wilson; Janet S. Rader; Behnaz Behmaram; Denise Uyar; William Bradley; John Wrangle; Alessandro Pastore; Douglas A. Levine; Fanny Dao; Jianjiong Gao; Nikolaus Schultz; Chris Sander; Marc Ladanyi; Mark Einstein; Randall Teeter; Stephen Benz; Nicolas Wentzensen; Ina Felau; Jean C. Zenklusen; Clara Bodelon; John A. Demchok; Liming Yang; Margi Sheth; Martin L. Ferguson; Roy Tarnuzzer; Hannah Yang; Mark Schiffman; Jiashan Zhang; Zhining Wang; Tanja Davidsen; Olayinka Olaniyan; Carolyn M. Hutter; Heidi J. Sofia; Dmitry A. Gordenin; Kin Chan; Steven A. Roberts; Leszek J. Klimczak; Carter Van Waes; Zhong Chen; Anthony D. Saleh; Hui Cheng; Jeremy Parfitt; John Bartlett; Monique Albert; Angel Arnaout; Harman Sekhon; Sebastien Gilbert; Myron Peto; Jerome Myers; Jodi Harr; John Eckman; Julie Bergsten; Kelinda Tucker; Leigh Anne Zach; Beth Y. Karlan; Jenny Lester; Sandra Orsulic; Qiang Sun; Rashi Naresh; Todd Pihl; Yunhu Wan; Howard Zaren; Jennifer Sapp; Judy Miller; Paul Drwiega; Kristen M. Leraas; Tara M. Lichtenberg; Erik Zmuda; Jay Bowen; Jessica Frick; Julie M. Gastier-Foster; Lisa Wise; Mark Gerken; Nilsa C. Ramirez; Ludmila Danilova; Leslie Cope; Stephen B. Baylin; Helga B. Salvesen; Christopher P. Vellano; Zhenlin Ju; Lixia Diao; Hao Zhao; Zechen Chong; Michael C. Ryan; Emmanuel Martinez-Ledesma; Roeland G. Verhaak; Lauren Averett Byers; Yuan Yuan; Ken Chen; Shiyun Ling; Gordon B. Mills; Yiling Lu; Rehan Akbani; Sahil Seth; Han Liang; Jing Wang; Leng Han; John N. Weinstein; Christopher A. Bristow; Wei Zhang; Harshad S. Mahadeshwar; Huandong Sun; Jiabin Tang; Jianhua Zhang; Xingzhi Song; Alexei Protopopov; Kenna R. Mills Shaw; Lynda Chin; Oluwole Olabode; Philip DiSaia; Amie Radenbaugh; David Haussler; Jingchun Zhu; Josh Stuart; Prabhakar Chalise; Devin Koestler; Brooke L. Fridley; Andrew K. Godwin; Rashna Madan; Giovanni Ciriello; Cathleen Martinez; Kelly Higgins; Therese Bocklage; J. Todd Auman; Charles M. Perou; Donghui Tan; Joel S. Parker; Katherine A. Hoadley; Matthew D. Wilkerson; Piotr A. Mieczkowski; Tara Skelly; Umadevi Veluvolu; D. Neil Hayes; W. Kimryn Rathmell; Alan P. Hoyle; Janae V. Simons; Junyuan Wu; Lisle E. Mose; Matthew G. Soloway; Saianand Balu; Shaowu Meng; Stuart R. Jefferys; Tom Bodenheimer; Yan Shi; Jeffrey Roach; Leigh B. Thorne; Lori Boice; Mei Huang; Corbin D. Jones; Rosemary Zuna; Joan Walker; Camille Gunderson; Carie Snowbarger; David Brown; Katherine Moxley; Kathleen Moore; Kelsi Andrade; Lisa Landrum; Robert Mannel; Scott McMeekin; Starla Johnson; Tina Nelson; Esther Elishaev; Rajiv Dhir; Robert Edwards; Rohit Bhargava; Daniel G. Tiezzi; Jurandyr M. Andrade; Houtan Noushmehr; Carlos Gilberto Carlotti; Daniela Pretti da Cunha Tirapelli; Daniel J. Weisenberger; David J. Van Den Berg; Dennis T. Maglinte; Moiz S. Bootwalla; Phillip H. Lai; Timothy Triche; Elizabeth M. Swisher; Kathy J. Agnew; Carl Simon Shelley; Peter W. Laird; Julie Schwarz; Perry Grigsby; David Mutch Show More Hide
Publisher(s):
Springer Nature; NATURE PUBLISHING GROUP
Tags:
Multidisciplinary; General
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article description
Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers.