Integration of HPV-DNA in the human genome : loss of gene function in cervica tumor cells as a consequence of HPV integration?

Integration of the HPV genome into the host chromatin is a frequent event in cervical cancer development. Viral integration sites serve as molecular markers for tumor clonality suggesting that integration as such provides the cell with a growth advantage. However, beyond the well documented constitutive expression of viral oncogenes in these tumors, HPV integration may also contribute to carcinogenesis by inactivating cellular genes relevant for cell homeostasis. Objective: We hypothesize that at least in some tumors viral insertional mutagenesis in combination with deletion or epigenetic modification of the second allele will have resulted in loss of gene function. Methods: We identified 47 HPV integration sites using an RNA based assay (APOT). Furthermore, we have pre- selected ten squamous cell carcinomas with specified attributes and analysed these also on DNA (DIPS) level. Of these selected samples, tissue sections were microdissected and analysed with a one-step RT-nested PCR to evaluate the presence of the transcript derived from the gene affected by HPV integration. For several tumors loss of gene expression could also be assessed by immunohistochemistry.


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