| Literature DB >> 24390348 |
Akinyemi I Ojesina1, Lee Lichtenstein2, Samuel S Freeman3, Chandra Sekhar Pedamallu4, Ivan Imaz-Rosshandler5, Trevor J Pugh4, Andrew D Cherniack3, Lauren Ambrogio3, Kristian Cibulskis3, Bjørn Bertelsen6, Sandra Romero-Cordoba5, Victor Treviño7, Karla Vazquez-Santillan5, Alberto Salido Guadarrama5, Alexi A Wright8, Mara W Rosenberg3, Fujiko Duke9, Bethany Kaplan4, Rui Wang10, Elizabeth Nickerson3, Heather M Walline11, Michael S Lawrence3, Chip Stewart3, Scott L Carter3, Aaron McKenna3, Iram P Rodriguez-Sanchez12, Magali Espinosa-Castilla5, Kathrine Woie13, Line Bjorge14, Elisabeth Wik14, Mari K Halle14, Erling A Hoivik14, Camilla Krakstad14, Nayeli Belem Gabiño5, Gabriela Sofia Gómez-Macías12, Lezmes D Valdez-Chapa12, María Lourdes Garza-Rodríguez12, German Maytorena15, Jorge Vazquez15, Carlos Rodea15, Adrian Cravioto15, Maria L Cortes3, Heidi Greulich16, Christopher P Crum17, Donna S Neuberg18, Alfredo Hidalgo-Miranda5, Claudia Rangel Escareno19, Lars A Akslen20, Thomas E Carey21, Olav K Vintermyr20, Stacey B Gabriel3, Hugo A Barrera-Saldaña12, Jorge Melendez-Zajgla5, Gad Getz22, Helga B Salvesen23, Matthew Meyerson24.
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.Entities:
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Year: 2013 PMID： 24390348 PMCID： PMC4161954 DOI： 10.1038/nature12881
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962