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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.

Titel:	Integrated genomic and molecular characterization of cervical cancer
Autor/in / Beteiligte Person:	Burk, Robert D ; Chen, Zigui ; Saller, Charles ; Tarvin, Katherine ; Carvalho, Andre L ; Scapulatempo-Neto, Cristovam ; Silveira, Henrique C ; Fregnani, José H ; Creighton, Chad J ; Anderson, Matthew L ; Castro, Patricia ; Wang, Sophia S ; Yau, Christina ; Benz, Christopher ; Robertson, A Gordon ; Mungall, Karen ; Lim, Lynette ; Bowlby, Reanne ; Sadeghi, Sara ; Brooks, Denise ; Sipahimalani, Payal ; Mar, Richard ; Ally, Adrian ; Clarke, Amanda ; Mungall, Andrew J ; Tam, Angela ; Lee, Darlene ; Chuah, Eric ; Schein, Jacqueline E ; Tse, Kane ; Kasaian, Katayoon ; Ma, Yussanne ; Marra, Marco A ; Mayo, Michael ; Balasundaram, Miruna ; Thiessen, Nina ; Dhalla, Noreen ; Carlsen, Rebecca ; Moore, Richard A ; Holt, Robert A ; Jones, Steven JM ; Wong, Tina ; Pantazi, Angeliki ; Parfenov, Michael ; Kucherlapati, Raju ; Hadjipanayis, Angela ; Seidman, Jonathan ; Kucherlapati, Melanie ; Ren, Xiaojia ; Xu, Andrew W ; Yang, Lixing ; Park, Peter J ; Lee, Semin ; Rabeno, Brenda ; Huelsenbeck-Dill, Lori ; Borowsky, Mark ; Cadungog, Mark ; Iacocca, Mary ; Petrelli, Nicholas ; Swanson, Patricia ; Ojesina, Akinyemi I ; Le, Xuan ; Sandusky, George ; Adebamowo, Sally N ; Akeredolu, Teniola ; Adebamowo, Clement ; Reynolds, Sheila M ; Shmulevich, Ilya ; Shelton, Candace ; Crain, Daniel ; Mallery, David ; Curley, Erin ; Gardner, Johanna ; Penny, Robert ; Morris, Scott ; Shelton, Troy ; Liu, Jia ; Lolla, Laxmi ; Chudamani, Sudha ; Wu, Ye ; Birrer, Michael ; McLellan, Michael D ; Bailey, Matthew H ; Miller, Christopher A ; Wyczalkowski, Matthew A ; Fulton, Robert S ; Fronick, Catrina C ; Lu, Charles ; Mardis, Elaine R ; Appelbaum, Elizabeth L ; Schmidt, Heather K ; Fulton, Lucinda A ; Cordes, Matthew G ; Li, Tiandao ; Ding, Li ; Wilson, Richard K ; Rader, Janet S ; Behmaram, Behnaz ; Uyar, Denise ; Bradley, William
Link:	View record in eScholarship (Volltext)
Zeitschrift:	Nature, Jg. 543 (2017-03-01), Heft 7645
Veröffentlichung:	eScholarship, University of California, 2017
Medientyp:	academicJournal
Umfang:	378 - 384
Schlagwort:	Biomedical and Clinical Sciences Oncology and Carcinogenesis Immunology Cervical Cancer Cancer Clinical Research Human Genome Sexually Transmitted Infections Biotechnology Genetics 2.1 Biological and endogenous factors Aetiology APOBEC-1 Deaminase Adenocarcinoma B7-H1 Antigen Carcinoma Squamous Cell Caspase 8 DNA-Binding Proteins Female Genomics HLA-A Antigens Human papillomavirus 16 Humans Keratins Mitogen-Activated Protein Kinase Kinases Molecular Targeted Therapy Mutation Nuclear Proteins PTEN Phosphohydrolase Phosphatidylinositol 3-Kinases Programmed Cell Death 1 Ligand 2 Protein Protein Serine-Threonine Kinases Proteomics Proto-Oncogene Proteins p21(ras) RNA Long Noncoding Receptor ErbB-3 Transforming Growth Factor-beta Type II Receptors Transforming Growth Factor beta Signal Transduction Transcription Factors Uterine Cervical Neoplasms Virus Integration Cancer Genome Atlas Research Network Albert Einstein College of Medicine Analytical Biological Services Barretos Cancer Hospital Baylor College of Medicine Beckman Research Institute of City of Hope Buck Institute for Research on Aging Canada's Michael Smith Genome Sciences Centre Harvard Medical School Helen F. Graham Cancer Center &Research Institute at Christiana Care Health Services HudsonAlpha Institute for Biotechnology ILSbio LLC Indiana University School of Medicine Institute of Human Virology Institute for Systems Biology International Genomics Consortium Leidos Biomedical Massachusetts General Hospital McDonnell Genome Institute at Washington University Medical College of Wisconsin Medical University of South Carolina Memorial Sloan Kettering Cancer Center Montefiore Medical Center NantOmics National Cancer Institute National Hospital Abuja Nigeria National Human Genome Research Institute National Institute of Environmental Health Sciences National Institute on Deafness &Other Communication Disorders Ontario Tumour Bank London Health Sciences Centre Ontario Institute for Cancer Research The Ottawa Hospital Oregon Health &Science University Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center SRA International St Joseph's Candler Health System Eli &Edythe L. Broad Institute of Massachusetts Institute of Technology &Harvard University Research Institute at Nationwide Children's Hospital Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University University of Bergen University of Texas MD Anderson Cancer Center University of Abuja Teaching Hospital University of Alabama at Birmingham University of California Irvine University of California Santa Cruz University of Kansas Medical Center University of Lausanne University of New Mexico Health Sciences Center University of North Carolina at Chapel Hill University of Oklahoma Health Sciences Center University of Pittsburgh University of São Paulo Ribeir ão Preto Medical School University of Southern California University of Washington University of Wisconsin School of Medicine &Public Health Van Andel Research Institute Washington University in St Louis erbB-3 General Science & Technology
Sonstiges:	Nachgewiesen in: eScholarship Document Type: article Rights: public

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Integrated genomic and molecular characterization of cervical cancer