Walline Heather M, Goudsmit Christine M, McHugh Jonathan B, Tang Alice L, Owen John H, Teh Bin T, McKean Erin, Glover Thomas W, Graham Martin P, Prince Mark E, Chepeha Douglas B, Chinn Steven B, Ferris Robert L, Gollin Susanne M, Hoffmann Thomas K, Bier Henning, Brakenhoff Ruud, Bradford Carol R, Carey Thomas E
Cancer Biology Program, Program in the Biomedical Sciences, Rackham Graduate School, University of Michigan, Ann Arbor, Michigan.
Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
Head Neck. 2017 May;39(5):840-852. doi: 10.1002/hed.24729. Epub 2017 Feb 25.
Human papillomavirus (HPV)-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16- and HPV18-positive squamous cell carcinoma lines.
E6/E7 alternate transcripts were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites.
All HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 head and neck squamous cell carcinoma (HNSCC) lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration.
HPV integration into cancer-related genes occurred in 7 of 9 HPV-positive cell lines and of these 6 were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors. © 2017 Wiley Periodicals, Inc. Head Neck 39: 840-852, 2017.
人乳头瘤病毒（HPV）阳性口咽癌通常对治疗反应良好，但一些HPV阳性肿瘤尽管接受了积极治疗仍会进展。本研究的目的是评估HPV16和HPV18阳性鳞状细胞癌系中的病毒癌基因表达和病毒整合位点。
通过逆转录聚合酶链反应（RT-PCR）评估E6/E7交替转录本。整合乳头瘤病毒序列检测（DIPS-PCR）和测序确定了病毒插入位点和受影响的宿主基因。在病毒整合位点评估细胞基因表达。
所有HPV阳性细胞系均表达交替的HPV E6/E7剪接，表明存在活跃的病毒致癌作用。在8个头颈鳞状细胞癌（HNSCC）系中，HPV整合发生在癌症相关基因TP63、DCC、JAK1、TERT、ATR、ETV6、PGR、PTPRN2和TMEM237内，但UM-SCC-105和UM-GCC-1仅有基因间整合。
9个HPV阳性细胞系中有7个发生了HPV整合到癌症相关基因中，其中6个来自进展的肿瘤。HPV整合到癌症相关基因中可能是HPV驱动肿瘤中的一种继发性致癌驱动因素。©2017威利期刊公司。头颈39: 840 - 852，2017。
