Human papillomavirus type 16 sub-lineages and integration in cancer [article]

Robert Jackson, Alejandro Ortigas-Vásquez, Ingeborg Zehbe
2020 bioRxiv   pre-print
Our lab has been intrigued by the fact that viral genomes often take on the role of mobile elements to perpetuate their existence in a complex organism's genome. Multiple DNA viruses such as Epstein-Barr virus, hepatitis B virus, and human papillomavirus (HPV) can invade their host genome, as "genomic parasites". We have been investigating HPV type 16 (HPV16), which is a prominent human tumour virus. In our recent in vitro work using 3D organoids, a common variant of HPV16's coding region
more » ... ed early integration into the host genome compared to the prototype. Next-generation sequencing (NGS) data confirmed a transcriptomic profile of increased proliferation and chromosomal instability−both hallmarks of cancer. Epidemiologically, this variant is associated with a high cervical cancer incidence. To substantiate in vitro findings and test variant-specific integration across HPV16-related cancers, we employed NGS data from population-derived clinical samples in The Cancer Genome Atlas (TCGA)-curated database. Data were analyzed for HPV16 positivity, sub-lineage, and viral-host integration using a bioinformatic pipeline of open-source tools, including HPVDetector. Here, we report the initial analysis for a subset of 37 cervical cancer cases comprised of HPV16 positive and negative samples as well as different sub-lineage and integration states. We do not presently find an association between sub-lineage and integration, but these determinations are confounded by discrepancies between DNA- and RNA-level data and the small sample size. We conclude by discussing challenges and future directions for analyzing the remaining TCGA cases−a requirement to increase statistical power. The overall goal is to investigate integration patterns quantitatively and qualitatively as well as to confirm or refute our initial hypothesis based on clinical sample data. Dissecting integration patterns of HPV sub-lineage genomes may uncover viral-host interactions evolutionarily related to transposable elements−a group of molecules increasingly identified in a wide array of functions within humans. The overall understanding of risk factors related to HPV sub-lineage could be relevant for prognostic and cancer treatment efficiency biomarkers.
doi:10.1101/2020.06.25.162958 fatcat:clwczn6a5fejddmyvncv242pcy