Characterization of HPV integration, viral gene expression and E6E7 alternative transcripts by RNA-Seq: A descriptive study in invasive cervical cancer

• Published in: Genomics (San Diego, Calif.) Vol. 111; no. 6; pp. 1853 - 1861
• Main Authors: Brant, Ayslan C., Menezes, Albert N., Felix, Shayany P., de Almeida, Liz M., Sammeth, Michael, Moreira, Miguel A.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2019
• Subjects: Alternative Splicing; Cervical cancer; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; E6E7 alternative transcripts; Female; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Viral; HPV expression; HPV genome integration; Human papillomavirus 16 - genetics; Human papillomavirus 16 - metabolism; Human papillomavirus 18 - genetics; Human papillomavirus 18 - metabolism; Humans; Oncogene Proteins, Viral - biosynthesis; Oncogene Proteins, Viral - genetics; Papillomavirus E7 Proteins - biosynthesis; Papillomavirus E7 Proteins - genetics; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; RNA-Seq; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; Virus Integration; HPV expression; Alternative splicing; HPV genome integration; Cervical cancer; E6E7 alternative transcripts
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2018.12.008

Scarce data are available on the expression of papillomavirus genome and the frequency of alternatively spliced E6E7 mRNAs in invasive cervical cancer. We carried out a comprehensive characterization of HPV expression by RNA-Seq analysis in 22 invasive cervical cancer with HPV16 or HPV18, characterizing the presence of integrated/episomal viral DNA, the integration sites in human genome and the proportion of alternative splicing products of E6 and E7 genes. The expression patterns suggested the presence of episomal and/or integrated viral DNA, with integration detected in most tumors, frequently occurring within human genes in HPV18+ and in intergenic regions in HPV16+ tumors. Alternative splicing of E6E7 transcripts showed E6*I as the most frequent isoform for both viral types, followed by E6*II and E6/E7 (unspliced) transcripts in HPV16+, and by E6/E7 in HPV18+ tumors. Previously described E6*VI and E6*V transcript isoforms for HPV16, and E6*X for HPV18, were rare or not detected. •Scarce data are available on the expression of HPV genes in cervical cancer.•We characterized by RNA-Seq, the HPV16 and HPV18 expression in cervical cancer and the splicing products of E6 and E7 genes.•The analysis suggested the presence of episomal and/or integrated viral DNA, with HPV18 recurrently integrated within genes.•E6*I was most frequent transcript isoform for both viral types.•The transcripts isoforms E6*VI and E6*V for HPV16, and E6*X for HPV18, were rare or not detected.