Landscape of genomic alterations in cervical carcinomas


Por: Ojesina A.I., Lichtenstein L., Freeman S.S., Pedamallu C.S., Imaz-Rosshandler I., Pugh T.J., Cherniack A.D., Ambrogio L., Cibulskis K., Bertelsen B., Romero-Cordoba S., Trevino, V, Vazquez-Santillan K., Guadarrama A.S., Wright A.A., Rosenberg M.W., Duke F., Kaplan B., Wang R., Nickerson E., Walline H.M., Lawrence M.S., Stewart C., Carter S.L., McKenna A., Rodriguez-Sanchez I.P., Espinosa-Castilla M., Woie K., Bjorge L., Wik E., Halle M.K., Hoivik E.A., Krakstad C., Gabino, NB, Gómez-Macías G.S., Valdez-Chapa L.D., Garza-Rodríguez M.L., Maytorena G., Vazquez J., Rodea C., Cravioto A., Cortes M.L., Greulich H., Crum C.P., Neuberg D.S., Hidalgo-Miranda A., Escareno C.R., Akslen L.A., Carey T.E., Vintermyr O.K., Gabriel S.B., Barrera-Saldaña H.A., Melendez-Zajgla J., Getz G., Salvesen H.B., Meyerson M.

Publicada: 20 feb 2014
Categoría: Multidisciplinary

Resumen:
Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide(1,2). The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established(3). Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS(4-7) as well as several copy-number alterations in the pathogenesis of cervical carcinomas(8,9). 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

Filiaciones:
Ojesina A.I.:
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States

 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Lichtenstein L.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Freeman S.S.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Pedamallu C.S.:
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States

 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Imaz-Rosshandler I.:
 Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico

Pugh T.J.:
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States

 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Cherniack A.D.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Ambrogio L.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Cibulskis K.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Bertelsen B.:
 Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway

Romero-Cordoba S.:
 Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico

Vazquez-Santillan K.:
 Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico

Guadarrama A.S.:
 Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico

Wright A.A.:
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States

 Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States

Rosenberg M.W.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Duke F.:
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States

Kaplan B.:
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States

 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Wang R.:
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States

 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China

Nickerson E.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Walline H.M.:
 Cancer Biology Program, Rackham Graduate School, University of Michigan, Ann Arbor, MI 48109, United States

Lawrence M.S.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Stewart C.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Carter S.L.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

McKenna A.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Rodriguez-Sanchez I.P.:
 Facultad de Medicina y Hospital Universitario 'Dr. José Eluterio González', Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, Mexico

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.:
 Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway

 Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway

Wik E.:
 Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway

 Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway

Halle M.K.:
 Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway

 Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway

Hoivik E.A.:
 Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway

 Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway

Krakstad C.:
 Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway

 Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway

Gómez-Macías G.S.:
 Facultad de Medicina y Hospital Universitario 'Dr. José Eluterio González', Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, Mexico

Valdez-Chapa L.D.:
 Facultad de Medicina y Hospital Universitario 'Dr. José Eluterio González', Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, Mexico

Garza-Rodríguez M.L.:
 Facultad de Medicina y Hospital Universitario 'Dr. José Eluterio González', Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, Mexico

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 M.L.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Greulich H.:
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States

 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

 Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States

Crum C.P.:
 Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, United States

Neuberg D.S.:
 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, United States

Hidalgo-Miranda A.:
 Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico

Escareno C.R.:
 Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico

 Claremont Graduate University, Claremont, CA 91711, United States

Akslen L.A.:
 Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway

 Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, N5020 Bergen, Norway

Carey T.E.:
 Head and Neck Oncology Program, Department of Otolaryngology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 38109, United States

Vintermyr O.K.:
 Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway

 Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, N5020 Bergen, Norway

Gabriel S.B.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

Barrera-Saldaña H.A.:
 Facultad de Medicina y Hospital Universitario 'Dr. José Eluterio González', Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, Mexico

Melendez-Zajgla J.:
 Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico

Getz G.:
 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

 Massachusetts General Hospital Cancer Center, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States

Salvesen H.B.:
 Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway

 Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway

Meyerson M.:
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States

 Eli and Edythe L. Broad Institute of Massachusetts, Institute of Technology, Harvard University, Cambridge, MA 02142, United States

 Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, United States

Tecnológico de Monterrey, Monterrey 64849, Mexico
ISSN: 00280836
Editorial
NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 506 Número: 7488
Páginas: 371-375
WOS Id: 000331477800042
ID de PubMed: 24390348
imagen All Open Access; Green

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