Integrated genomic and molecular characterization of cervical cancer

Autor:	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 Tumour Bank, Ontario Institute for Cancer Research, Ontario Tumour Bank, 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
Rok vydání:	2017
Předmět:	Medical College of Wisconsin Proteomics Cedars-Sinai Medical Center National Cancer Institute Oregon Health &Science University University of New Mexico Health Sciences Center Cancer Genome Atlas Research Network Canada's Michael Smith Genome Sciences Centre National Hospital National Institute on Deafness &Other Communication Disorders Van Andel Research Institute Transforming Growth Factor beta ErbB-3 Molecular Targeted Therapy Aetiology Cancer Human papillomavirus 16 University of Lausanne Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University Genomics University of Texas MD Anderson Cancer Center Samuel Oschin Comprehensive Cancer Institute Harvard Medical School LLC Helen F. Graham Cancer Center &Research Institute at Christiana Care Health Services Buck Institute for Research on Aging Nigeria Indiana University School of Medicine Adenocarcinoma Proto-Oncogene Proteins p21(ras) University of California Ontario Institute for Cancer Research Clinical Research University of Alabama at Birmingham Genetics Humans Barretos Cancer Hospital University of California Santa Cruz Baylor College of Medicine University of Washington Ribeir ão Preto Medical School University of Bergen Programmed Cell Death 1 Ligand 2 Protein Beckman Research Institute of City of Hope University of North Carolina at Chapel Hill Mutation Research Institute at Nationwide Children's Hospital Sexually Transmitted Infections Eli &Edythe L. Broad Institute of Massachusetts Institute of Technology &Harvard University ILSbio Transcription Factors Transforming Growth Factor-beta Type II Uterine Cervical Neoplasms Analytical Biological Services Cervical Cancer B7-H1 Antigen National Human Genome Research Institute London Health Sciences Centre Phosphatidylinositol 3-Kinases Receptors Institute for Systems Biology 2.1 Biological and endogenous factors McDonnell Genome Institute at Washington University Irvine University of Oklahoma Health Sciences Center Caspase 8 University of São Paulo Nuclear Proteins University of Pittsburgh Protein-Serine-Threonine Kinases DNA-Binding Proteins NantOmics Memorial Sloan Kettering Cancer Center Keratins Female Long Noncoding SRA International Leidos Biomedical HudsonAlpha Institute for Biotechnology Receptor Signal Transduction Biotechnology General Science & Technology University of Abuja Teaching Hospital Virus Integration APOBEC-1 Deaminase Medical University of South Carolina Protein Serine-Threonine Kinases Albert Einstein College of Medicine Abuja International Genomics Consortium National Institute of Environmental Health Sciences Massachusetts General Hospital University of Kansas Medical Center Mitogen-Activated Protein Kinase Kinases HLA-A Antigens The Ottawa Hospital Carcinoma Human Genome PTEN Phosphohydrolase Ontario Tumour Bank University of Wisconsin School of Medicine &Public Health Squamous Cell St Joseph's Candler Health System University of Southern California Washington University in St Louis RNA Montefiore Medical Center Institute of Human Virology
Zdroj:	Nature, vol 543, iss 7645
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::0e44b69213d674d6e55a8352e5ba7565 https://escholarship.org/uc/item/1j13q58s Zobrazit plný text záznamu