Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma.
Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma.
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DOI：
10.18632/oncotarget.15179
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发表时间：
2017-03-14
期刊：
影响因子：
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通讯作者：
Windle B
中科院分区：
文献类型：
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作者：
Nulton TJ;Olex AL;Dozmorov M;Morgan IM;Windle B
人乳头瘤病毒（HPV）DNA在高达80%的口咽癌（OPC）中被检测到，并且这种HPV阳性疾病已经达到流行比例。为了增加我们对这种疾病的理解，我们研究了HPV阳性头颈癌（HNC）中HPV 16基因组的状态。分析来自癌症基因组图谱HNC样本的原始RNA-Seq和全基因组序列数据，以全面了解这些肿瘤的HPV基因组状态。在这一分析之后，提出了几个显著和新颖的观察结果。首先，在这些肿瘤中有三种主要的HPV基因组状态，它们相对均匀地分裂：仅附加体状态，整合状态和病毒基因组作为与人类DNA的杂合附加体存在的状态。其次，没有肿瘤表达高水平的E6; E6*I是所有肿瘤中表达的优势变体。这项研究最引人注目的结论是，大约四分之三的HPV 16阳性HNC含有病毒基因组的附加型版本，这些病毒基因组可能以E1-E2依赖的方式复制。这些观察结果的临床和治疗意义进行了讨论。
Human papillomavirus (HPV) DNA is detected in up to 80% of oropharyngeal carcinomas (OPC) and this HPV positive disease has reached epidemic proportions. To increase our understanding of the disease, we investigated the status of the HPV16 genome in HPV-positive head and neck cancers (HNC). Raw RNA-Seq and Whole Genome Sequence data from The Cancer Genome Atlas HNC samples were analyzed to gain a full understanding of the HPV genome status for these tumors. Several remarkable and novel observations were made following this analysis. Firstly, there are three main HPV genome states in these tumors that are split relatively evenly: An episomal only state, an integrated state, and a state in which the viral genome exists as a hybrid episome with human DNA. Secondly, none of the tumors expressed high levels of E6; E6*I is the dominant variant expressed in all tumors. The most striking conclusion from this study is that around three quarters of HPV16 positive HNC contain episomal versions of the viral genome that are likely replicating in an E1-E2 dependent manner. The clinical and therapeutic implications of these observations are discussed.