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Human papillomavirus and the landscape of secondary genetic alterations in oral cancers.
Gillison, Maura L; Akagi, Keiko; Xiao, Weihong; Jiang, Bo; Pickard, Robert K L; Li, Jingfeng; Swanson, Benjamin J; Agrawal, Amit D; Zucker, Mark; Stache-Crain, Birgit; Emde, Anne-Katrin; Geiger, Heather M; Robine, Nicolas; Coombes, Kevin R; Symer, David E.
Afiliación
  • Gillison ML; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Akagi K; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Xiao W; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Jiang B; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Pickard RKL; Division of Medical Oncology, Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210, USA.
  • Li J; Division of Medical Oncology, Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210, USA.
  • Swanson BJ; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
  • Agrawal AD; Department of Otolaryngology - Head and Neck Surgery, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
  • Zucker M; Department of Biomedical Informatics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
  • Stache-Crain B; Complete Genomics, Mountain View, California 95134, USA.
  • Emde AK; New York Genome Center, New York, New York 10013, USA.
  • Geiger HM; New York Genome Center, New York, New York 10013, USA.
  • Robine N; New York Genome Center, New York, New York 10013, USA.
  • Coombes KR; Department of Biomedical Informatics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
  • Symer DE; Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Genome Res ; 29(1): 1-17, 2019 01.
Article en En | MEDLINE | ID: mdl-30563911
Human papillomavirus (HPV) is a necessary but insufficient cause of a subset of oral squamous cell carcinomas (OSCCs) that is increasing markedly in frequency. To identify contributory, secondary genetic alterations in these cancers, we used comprehensive genomics methods to compare 149 HPV-positive and 335 HPV-negative OSCC tumor/normal pairs. Different behavioral risk factors underlying the two OSCC types were reflected in distinctive genomic mutational signatures. In HPV-positive OSCCs, the signatures of APOBEC cytosine deaminase editing, associated with anti-viral immunity, were strongly linked to overall mutational burden. In contrast, in HPV-negative OSCCs, T>C substitutions in the sequence context 5'-ATN-3' correlated with tobacco exposure. Universal expression of HPV E6*1 and E7 oncogenes was a sine qua non of HPV-positive OSCCs. Significant enrichment of somatic mutations was confirmed or newly identified in PIK3CA, KMT2D, FGFR3, FBXW7, DDX3X, PTEN, TRAF3, RB1, CYLD, RIPK4, ZNF750, EP300, CASZ1, TAF5, RBL1, IFNGR1, and NFKBIA Of these, many affect host pathways already targeted by HPV oncoproteins, including the p53 and pRB pathways, or disrupt host defenses against viral infections, including interferon (IFN) and nuclear factor kappa B signaling. Frequent copy number changes were associated with concordant changes in gene expression. Chr 11q (including CCND1) and 14q (including DICER1 and AKT1) were recurrently lost in HPV-positive OSCCs, in contrast to their gains in HPV-negative OSCCs. High-ranking variant allele fractions implicated ZNF750, PIK3CA, and EP300 mutations as candidate driver events in HPV-positive cancers. We conclude that virus-host interactions cooperatively shape the unique genetic features of these cancers, distinguishing them from their HPV-negative counterparts.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias de la Boca / Carcinoma de Células Escamosas / Proteínas Oncogénicas Virales / Infecciones por Papillomavirus / Proteínas de Neoplasias Tipo de estudio: Clinical_trials / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Genome Res Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2019 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias de la Boca / Carcinoma de Células Escamosas / Proteínas Oncogénicas Virales / Infecciones por Papillomavirus / Proteínas de Neoplasias Tipo de estudio: Clinical_trials / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Genome Res Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2019 Tipo del documento: Article