Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions
- 17 January 2002
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 21 (3), 419-426
- https://doi.org/10.1038/sj.onc.1205104
Abstract
Persistent high risk type human papillomavirus (HR-HPVs) infections induce dysplasia or cancer of the anogenital tract, most notably of the uterine cervix. The viral genome usually persists and replicates as an episomal molecule in early dysplasia, whereas in advanced dysplasia or cervical cancer HPV genomes are frequently integrated into the chromosomal DNA of the host cell. Previous studies suggested that modification of critical cellular sequences by integration of HPV genomes might significantly contribute to the neoplastic transformation of anogenital epithelia (insertional mutagenesis). This prompted us to characterize the integration loci of high risk HPV genomes in a large set of genital lesions. We amplified E6/E7 oncogene transcripts derived from integrated HPV16 and HPV18 genomes and characterized in detail the co-transcribed cellular sequences of 64 primary genital lesions and five cervical cancer cell lines. Database analyses of the cellular parts of these fusion transcripts revealed 51 different integration loci, including 26 transcribed genes (14 known genes, 12 EST sequences with unknown gene function). Seventeen sequences showed similarity to repetitive elements, and 26 sequences did not show any database match other than genomic sequence. Chromosomal integration loci were distributed over almost all human chromosomes. Although we found HPV sequences integrated into cancer related genes and close to fragile sites, no preferential site or integration motif could be identified. These data demonstrate that target directed insertional mutagenesis might occur in few HPV-induced anogenital lesions, however, it is rather the exception than the rule.Keywords
This publication has 32 references indexed in Scilit:
- Function of the c-Myc oncoprotein in chromatin remodeling and transcriptionBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2001
- The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycleProceedings of the National Academy of Sciences of the United States of America, 2000
- The molecular genetics of cervical carcinomaBritish Journal of Cancer, 1999
- Use of the polymerase chain reaction to specifically amplify integrated HPV-16 DNA by virtue of its linkage to interspersed repetitive DNAMolecular and Cellular Probes, 1996
- Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemiaNature Genetics, 1996
- Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis.Proceedings of the National Academy of Sciences of the United States of America, 1995
- Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas.Proceedings of the National Academy of Sciences of the United States of America, 1993
- Basic local alignment search toolJournal of Molecular Biology, 1990
- Structure and Expression of an Integrated Human Papillomavirus Type 16 Genome Amplified in a Cervical Carcinoma Cell LineJournal of General Virology, 1989
- Regional chromosome localization of human papillomavirus intergration sites near fragile sites, oncogenes, and cancer chromosome breakpointsCancer Genetics and Cytogenetics, 1988