HPV is like a tornado, destroying the host cell genome

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Genomic instability is one of the characteristics of cancer, including those caused by human papillomavirus (HPV). Researchers from Ohio State University recently published an article in "Genome Research", which reported a surprising association between HPV integration and structural variation in adjacent host genomes.

The team used genome sequencing to identify mutation patterns in more than a dozen cell lines and primary tumors. They not only represent HPV-positive cervical cancer, but also HPV-negative and positive cancers of the head and neck. The analysis results show that there are a lot of structural changes, rearrangements and / or mutations around the HPV insertion site in the genome. The author suspects that this may be due to the "circular" interaction between the virus and the host DNA.

Corresponding author of the article, David Symer, a researcher at the Ohio State University Comprehensive Cancer Center, said: "HPV is like a tornado that attacks the genome, destroying and rearranging the genes of surrounding host cells. This leads to overexpression of oncogenes, or tumor suppression Gene damage. Both types of damage may promote cancer development.

Past studies have shown that HPV proteins E6 and E7 promote cancer development by interfering with the function of tumor suppressor genes such as TP53. However, the genomic changes associated with HPV infection, including those that cause cancer, are still not very clear.

To better understand the interaction between HPV and host DNA, Symer and colleagues used Illumina's HiSeq 2000 to sequence the genomic DNA of 10 cell lines: 2 HPV16-positive cervical cancer cell lines and 5 HPV16-positive Of head and neck squamous cell carcinoma (HNSCC) cells, and three HNSCC cells without HPV.

At the same time, the research team also added genomic sequence information of two primary HNSCC tumors, which were infected with HPV16 or HPV18, as well as RNA sequencing maps, spectral karyotype analysis results, and fluorescence in situ hybridization information.

In these data, the researchers focused on genetic changes caused by virus integration. In addition to looking for insertion breakpoints, they also analyzed the impact of such insertions on viral and host sequences and their expression.

In samples with multiple copies of the HPV genome, the researchers detected various variations near the host genome, from translocation and inversion to amplification and deletion.

Although more research is needed to clarify this process, the researchers speculate that structural changes related to HPV integration may result from the interaction between the virus and the host DNA. This so-called looping model "proposes a framework that helps to understand how HPV integrants in human cancer are surrounded by CNV."

The researchers also continue to study this circulating pattern in other HPV-related primary tumors and evaluate the significance of these genomic changes for the development of cervical cancer, targeted therapy, and patient treatment.

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