Human and HPV Genes Combine to Form Extrachromosomal DNA That Promotes Oropharyngeal Tumor Growth
EcDNA is made up of small, circular segments of DNA that form outside of chromosomes within the cell, and is frequently found in cancer cells. It has been shown to elude the immune system and drive carcinogenesis. Previous studies have demonstrated that ecDNA formed by the integration of HPV genes and human DNA is present in about 30% of HPV-positive oropharyngeal cancers. The study objective was to understand the molecular mechanisms by which hybrid ecDNA drives oropharyngeal cancer development.
The researchers analyzed changes to gene expression in ecDNA formed by HPV and human DNA hybridization in oropharyngeal tumor cells. The study discovered that:
Previously unidentified HPV and human DNA enhancers increased the expression of tumor-promoting genes in cancer cells, leading to the production of more of the virus and increasing tumor growth.
Targeting these enhancers with CRISPR gene editing technology and with proteins that regulate gene activity reduced their expression and inhibited growth in HPV-positive oropharyngeal tumors.
