A comprehensive analysis of HPV integration loci in anogenital lesions combining transcript and genome-based amplification techniques

摘要: Persistent infections with high-risk human papillomaviruses (HPVs) induce dysplastic lesions of the lower genital tract. Some these eventually progress to invasive cancers, particularly uterine cervix. In many advanced preneoplastic cervical and most derived carcinomas, HPV genomes are found be integrated into host cell chromosomes. Although integration seems play an important role in progression dysplasia, underlying mechanisms still unclear. To investigate pathogenic genomic greater detail, we analysed sites HPV16 18 21 anogenital precancerous cancerous using a ligation-mediated chain reaction (DIPS) recently described amplification papilloma virus oncogene transcripts (APOT) assay. On level, only singular events were observed individual neoplastic clones. At sites, short overlap between sequences was observed, suggesting that is mediated by nonhomologous sequence-specific recombination. APOT analysis revealed majority actively transcribed. These data suggest preneoplasia viral occurs at single or few chromosomal loci given clone. Disruption cellular genes might support malignant transformation rare cases; however, it not prerequisite. The main function stabilization transcription.