Methylation of CpG sites in the upstream regulatory region, physical status and mRNA expression of HPV-6 in adult-onset laryngeal papilloma

作者：Deng, Zeyi^*; Ikegami, Taro; Kiyuna, Asanori; Zhang, Chunlin; Zhang, Tao; Matayoshi, Sen; Uehara, Takayuki; Maeda, Hiroyuki; Suzuki, Mikio; Ganaha, Akira

来源：Oncotarget, 2017, 8(49): 85368-85377.

DOI：10.18632/oncotarget.19898

• adult-onset laryngeal papilloma
• human papillomavirus-6
• methylation
• physical status
• mRNA expression

The methylation status of HPV-6 upstream regulatory region (URR) in adult-onset laryngeal papillomatosis (AO-LP) remains unclear. The purpose of this study was to investigate the methylation status of URR and the physical status of HPV-6, as well as the dynamic variations of viral load and mRNA expression in AO-LP. We examined 18 specimens from 11 patients with AO-LP by real-time polymerase chain reaction (PCR), bisulfite-sequencing PCR, and amplification of papilloma oncogene transcripts. HPV-6 was identified in 9 of 11 patients (81.8%), and all the 15 specimens derived from 9 HPV-6-positive cases contained only episomal HPV-6 transcripts with intact E2. Three HPV-6-positive patients developed recurrent lesions, and HPV-6 copy numbers and mRNA expression decreased after surgical treatment. Among the 96 CpG sites (16/case), 67 (69.8%) were unmethylated, while 23 (30.2%) were heterogeneous (>= 1 methylated CpG clone). High viral loads and episomal status of HPV-6 were frequently observed in AO-LP; thus, persistent E6/E7 mRNA expression of LR-HPV-6 may be associated with AO-LP recurrences. Hypomethylation and scattered patterns of methylated CpGs at the URR of HPV-6 were identified in AO-LP.

• 出版日期2017-10-17
• 单位南方医科大学; 遵义医科大学