Oncotarget

Research Papers:

Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma

Tara J. Nulton, Amy L. Olex, Mikhail Dozmorov, Iain M. Morgan _ and Brad Windle

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Oncotarget. 2017; 8:17684-17699. https://doi.org/10.18632/oncotarget.15179

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Abstract

Tara J. Nulton1, Amy L. Olex2, Mikhail Dozmorov2,3, Iain M. Morgan1,4 and Brad Windle1,4,5

1 Department of Oral and Craniofacial Molecular Biology, VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Richmond, VA, USA

2 C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA

3 Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA

4 Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA

5 Department of Internal Medicine, Division of Hematology, Oncology and Palliative Care, Virginia Commonwealth University, Richmond, VA, USA

Correspondence to:

Iain M. Morgan, email:

Brad Windle, email:

Keywords: HPV16, head and neck cancer, TCGA, integration, genomic structure

Received: January 21, 2017 Accepted: January 25, 2017 Published: February 07, 2017

Abstract

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.


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