دورية أكاديمية
أعرض في EDS

Diverse tumorigenic consequences of human papillomavirus integration in primary oropharyngeal cancers.

التفاصيل البيبلوغرافية
العنوان: Diverse tumorigenic consequences of human papillomavirus integration in primary oropharyngeal cancers.
المؤلفون: Symer DE; Department of Lymphoma and Myeloma, 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., Geiger HM; New York Genome Center, New York, New York 10013, USA., Song Y; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Li G; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Emde AK; New York Genome Center, New York, New York 10013, 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., Corvelo A; New York Genome Center, New York, New York 10013, USA., Toussaint NC; New York Genome Center, New York, New York 10013, USA., Li J; Division of Medical Oncology, Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210, USA., Agrawal A; Department of Otolaryngology - Head and Neck Surgery, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA., Ozer E; Department of Otolaryngology - Head and Neck Surgery, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA., El-Naggar AK; Division of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Du Z; Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Shewale JB; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Stache-Crain B; Complete Genomics, San Jose, California 95134, USA., Zucker M; Department of Biomedical Informatics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, 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., Gillison ML; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
المصدر: Genome research [Genome Res] 2022 Jan; Vol. 32 (1), pp. 55-70. Date of Electronic Publication: 2021 Dec 13.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9518021 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-5469 (Electronic) Linking ISSN: 10889051 NLM ISO Abbreviation: Genome Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cold Spring Harbor, N.Y. : Cold Spring Harbor Laboratory Press, c1995-
مواضيع طبية MeSH: Alphapapillomavirus*/metabolism , Oncogene Proteins, Viral*/genetics , Oropharyngeal Neoplasms*/genetics, Carcinogenesis ; Humans ; Papillomaviridae/genetics ; Papillomaviridae/metabolism ; Papillomavirus E7 Proteins/genetics ; Papillomavirus E7 Proteins/metabolism ; Virus Integration/genetics
مستخلص: Human papillomavirus (HPV) causes 5% of all cancers and frequently integrates into host chromosomes. The HPV oncoproteins E6 and E7 are necessary but insufficient for cancer formation, indicating that additional secondary genetic events are required. Here, we investigate potential oncogenic impacts of virus integration. Analysis of 105 HPV-positive oropharyngeal cancers by whole-genome sequencing detects virus integration in 77%, revealing five statistically significant sites of recurrent integration near genes that regulate epithelial stem cell maintenance (i.e., SOX2, TP63, FGFR, MYC ) and immune evasion (i.e., CD274 ). Genomic copy number hyperamplification is enriched 16-fold near HPV integrants, and the extent of focal host genomic instability increases with their local density. The frequency of genes expressed at extreme outlier levels is increased 86-fold within ±150 kb of integrants. Across 95% of tumors with integration, host gene transcription is disrupted via intragenic integrants, chimeric transcription, outlier expression, gene breaking, and/or de novo expression of noncoding or imprinted genes. We conclude that virus integration can contribute to carcinogenesis in a large majority of HPV-positive oropharyngeal cancers by inducing extensive disruption of host genome structure and gene expression.
(© 2022 Symer et al.; Published by Cold Spring Harbor Laboratory Press.)
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معلومات مُعتمدة: P30 CA016672 United States CA NCI NIH HHS; R50 CA211533 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Oncogene Proteins, Viral)
0 (Papillomavirus E7 Proteins)
تواريخ الأحداث: Date Created: 20211214 Date Completed: 20220310 Latest Revision: 20230417
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8744672
DOI: 10.1101/gr.275911.121
PMID: 34903527
قاعدة البيانات: MEDLINE
الوصف
تدمد:1549-5469
DOI:10.1101/gr.275911.121