Abstract
Objective: Integration of HPV DNA into the host genome is a frequent event in cervical carcinogenesis. Viral integration sites seem to be randomly distributed among all chromosomes with a clear preference for genomic fragile sites. To date about 200 HPV DNA integration sites have been mapped. However, this number is still too small to fully comprehend the different mechanisms by which HPV DNA integration contributes to carcinogenesis. Methods: 55 cervical carcinoma samples of FIGO stage IA to IIIB positive for either HPV16 (n=34) or HPV18 (n=21) were analysed. Viral-cellular fusion transcripts were detected using the APOT assay (amplification of papillomavirus oncogene transcripts) introduced by Klaes and colleagues (Klaes et al., 1999). All putative viral-cellular fusion transcripts were analysed by sequencing. The genomic localisation of the integration sites were determined by database query of all available public databases. Results: The detection rate of viral-cellular fusion transcripts from HPV16 positive tumours was significantly lower (p=0.012, two-sided t-test) than that of HPV18 positive tumours (53% versus 81%, respectively). A BLASTN comparison of the fusion transcripts with the NCBI Database showed homology in 16 out of 35 cases, with 10 fusion transcripts containing known genes and 6 transcripts containing parts of Expressed Sequence Tags (EST). 16 integration sites were mapped within hypothetical genes listed in the UCSC Genome Browser Database. Conclusion: One striking finding of this study is the high proportion of viral integration sites within in silico predicted genes (46%). In contrast, only 29% of integration sites were located within known genes. This not only suggests that virus integration occurs within transcriptionally active chromosomal sites, but also that the APOT assay may be a useful tool for the detection of hypothetical genes which have not been analysed in the context of carcinogenesis thus far.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
