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Landscape of genomic alterations in cervical carcinomas.
Ojesina, Akinyemi I; Lichtenstein, Lee; Freeman, Samuel S; Pedamallu, Chandra Sekhar; Imaz-Rosshandler, Ivan; Pugh, Trevor J; Cherniack, Andrew D; Ambrogio, Lauren; Cibulskis, Kristian; Bertelsen, Bjørn; Romero-Cordoba, Sandra; Treviño, Victor; Vazquez-Santillan, Karla; Guadarrama, Alberto Salido; Wright, Alexi A; Rosenberg, Mara W; Duke, Fujiko; Kaplan, Bethany; Wang, Rui; Nickerson, Elizabeth; Walline, Heather M; Lawrence, Michael S; Stewart, Chip; Carter, Scott L; McKenna, Aaron; Rodriguez-Sanchez, Iram P; Espinosa-Castilla, Magali; Woie, Kathrine; Bjorge, Line; Wik, Elisabeth; Halle, Mari K; Hoivik, Erling A; Krakstad, Camilla; Gabiño, Nayeli Belem; Gómez-Macías, Gabriela Sofia; Valdez-Chapa, Lezmes D; Garza-Rodríguez, María Lourdes; Maytorena, German; Vazquez, Jorge; Rodea, Carlos; Cravioto, Adrian; Cortes, Maria L; Greulich, Heidi; Crum, Christopher P; Neuberg, Donna S; Hidalgo-Miranda, Alfredo; Escareno, Claudia Rangel; Akslen, Lars A; Carey, Thomas E; Vintermyr, Olav K.
Afiliação
  • Ojesina AI; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [3].
  • Lichtenstein L; 1] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [2].
  • Freeman SS; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Pedamallu CS; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Imaz-Rosshandler I; Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico.
  • Pugh TJ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Cherniack AD; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Ambrogio L; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Cibulskis K; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Bertelsen B; Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway.
  • Romero-Cordoba S; Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico.
  • Treviño V; Tecnológico de Monterrey, Monterrey 64849, Mexico.
  • Vazquez-Santillan K; Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico.
  • Guadarrama AS; Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico.
  • Wright AA; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
  • Rosenberg MW; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Duke F; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
  • Kaplan B; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Wang R; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
  • Nickerson E; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Walline HM; Cancer Biology Program, Program in the Biomedical Sciences, Rackham Graduate School, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Lawrence MS; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Stewart C; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Carter SL; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • McKenna A; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Rodriguez-Sanchez IP; Facultad de Medicina y Hospital Universitario 'Dr. José Eluterio González' de la Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, México.
  • Espinosa-Castilla M; Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico.
  • Woie K; Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway.
  • Bjorge L; 1] Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway [2] Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway.
  • Wik E; 1] Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway [2] Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway.
  • Halle MK; 1] Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway [2] Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway.
  • Hoivik EA; 1] Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway [2] Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway.
  • Krakstad C; 1] Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway [2] Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway.
  • Gabiño NB; Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico.
  • Gómez-Macías GS; Facultad de Medicina y Hospital Universitario 'Dr. José Eluterio González' de la Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, México.
  • Valdez-Chapa LD; Facultad de Medicina y Hospital Universitario 'Dr. José Eluterio González' de la Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, México.
  • Garza-Rodríguez ML; Facultad de Medicina y Hospital Universitario 'Dr. José Eluterio González' de la Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, México.
  • Maytorena G; Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico.
  • Vazquez J; Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico.
  • Rodea C; Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico.
  • Cravioto A; Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico.
  • Cortes ML; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Greulich H; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [3] Department of Medicine, Brigham and Women's Hospital, B
  • Crum CP; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
  • Neuberg DS; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
  • Hidalgo-Miranda A; Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico.
  • Escareno CR; 1] Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico [2] Claremont Graduate University, Claremont, California 91711, USA.
  • Akslen LA; 1] Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway [2] Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, N5020 Bergen, Norway.
  • Carey TE; Head and Neck Oncology Program and Department of Otolaryngology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 38109, USA.
  • Vintermyr OK; 1] Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway [2] Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, N5020 Bergen, Norway.
Nature ; 506(7488): 371-5, 2014 Feb 20.
Article em En | MEDLINE | ID: mdl-24390348
ABSTRACT
Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide. The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established. Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as several copy-number alterations in the pathogenesis of cervical carcinomas. Here we report whole-exome sequencing analysis of 115 cervical carcinoma-normal paired samples, transcriptome sequencing of 79 cases and whole-genome sequencing of 14 tumour-normal pairs. Previously unknown somatic mutations in 79 primary squamous cell carcinomas include recurrent E322K substitutions in the MAPK1 gene (8%), inactivating mutations in the HLA-B gene (9%), and mutations in EP300 (16%), FBXW7 (15%), NFE2L2 (4%), TP53 (5%) and ERBB2 (6%). We also observe somatic ELF3 (13%) and CBFB (8%) mutations in 24 adenocarcinomas. Squamous cell carcinomas have higher frequencies of somatic nucleotide substitutions occurring at cytosines preceded by thymines (Tp*C sites) than adenocarcinomas. Gene expression levels at HPV integration sites were statistically significantly higher in tumours with HPV integration compared with expression of the same genes in tumours without viral integration at the same site. These data demonstrate several recurrent genomic alterations in cervical carcinomas that suggest new strategies to combat this disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Genoma Humano / Neoplasias do Colo do Útero / Mutação Tipo de estudo: Observational_studies / Risk_factors_studies Idioma: En Revista: Nature Ano de publicação: 2014 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Genoma Humano / Neoplasias do Colo do Útero / Mutação Tipo de estudo: Observational_studies / Risk_factors_studies Idioma: En Revista: Nature Ano de publicação: 2014 Tipo de documento: Article