Regional chromosome localization of human papillomavirus intergration sites near fragile sites, oncogenes, and cancer chromosome breakpoints

Cannizzaro, Linda A.; Dürst, Matthias; Mendez, Michael J.; Hecht, Barbara K.; Hecht, Frederick

doi:10.1016/0165-4608(88)90054-4

Cited by 89 publications

(52 citation statements)

References 7 publications

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“…This strongly suggests that integration at those particular sites might have conferred some growth advantages to the cells and might have thus been crucial in their immortalization and their selection. In agreement with our results, in situ hybridization analyses on chromosomes have described HPV-16 or -18 integrated at a single site within cervical carcinomas [30] or cervical carcinoma cells such as SW756 [31], SiHa [32] or C4-I [33] cell lines, even though HeLa and Caski cells were shown to harbor HPV-18 and HPV-16 respectively at several distinct sites [32,34,35]. From those localization studies, it appeared that HPV integration sites were frequently mapped in regions containing oncogenes or fragile sites [10,11].…”

Section: Discussionsupporting

confidence: 81%

Viral integration sites in human papilloma virus-33-immortalized cervical keratinocyte cell lines

Gilles

Piette

Ploton

et al. 1996

Cancer Genetics and Cytogenetics

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The viral organization of HPV-33 was determined by Southern blotting in 2 HPV-33-immortalized cervical cell lines (CK11 and CK12) and compared to our previous results obtained on 10 other already characterized HPV-33-immortalized cell lines (CK1 to CK10). As observed in CK1 to CK10, the viral DNA was found integrated in the cellular genome of CK11 and CK12. However, in CK11 and CK12, the integrated viral genome was deleted and mostly limited to the URR and the E6-E7 ORFs, stressing the importance of those sequences in the immortalization process. Furthermore, CKll and CK12 showed a unique and identical integration site, as observed in CK1 to CK10, which also harbored HPV-33 integrated at a unique and identical site (which was however different from the one evidenced in CK11 and CK12). Indeed, in situ hybridizations on chromosomes allowed the precise localization of the viral DNA on chromosome 13q33-34 in CK1 to CK10 whereas it was mapped to chromosome 9p13 in CK11 and CK12. We discuss the possibility that integration of HPV-33 at those two particular sites has conferred some growth advantages to the cells and could have thus played a crucial role in the immortalization.

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Section: Discussionsupporting

confidence: 81%

Viral integration sites in human papilloma virus-33-immortalized cervical keratinocyte cell lines

Gilles

Piette

Ploton

et al. 1996

Cancer Genetics and Cytogenetics

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“…Unlike multicellular organisms, the early two-cell embryo either had only two copies of the genome that became disrupted by the HPV DNA or it lacked the necessary repair mechanism to correct for the integrated HPV DNA. The sites for HPV DNA integration into the host genome have been reported to be near oncogenes (27) causing transformation of cells, or at the chromosomal fragile site (28)(29)(30)(31)(32) at 3p14 (31,33) and the FRA8C site at 8q24 (34) resulting in gene interruption and loss of chromosome heterozygosity (24,35). Indirect evidence linking HPV infection and embryo demise would be the prevalence of HPV infection in the infertile population.…”

Section: Discussionmentioning

confidence: 99%

Human papilloma virus DNA exposure and embryo survival is stage-specific

Henneberg

Patton

Jacobson

et al. 2006

J Assist Reprod Genet

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Purpose: Human papillomavirus (HPV) has been shown to disrupt late-stage implanting embryos. The objectives were (a) to assess the development of early embryos exposed to HPV DNA and (b) to analyze the blastocyst hatching process after HPV exposure. Methods:The study involved exposing two-cell and 4-8-cell mouse embryos to DNA fragments from either HPV type 16, type 18 or DQA1 (control). The embryos were incubated for 120 h and assessed. Results: HPV 16 and 18 inhibited two-cell embryo development. In contrast, delaying the exposure of HPV DNA until the 4-8-cell stage resulted in further embryonic development. There was 25.9% less blastocyst formed with HPV 16 exposure. Additionally, there were 25.9-31.8% more degenerated embryos with HPV 16 exposure. Conclusions:The study demonstrated embryo stage-specific effects of HPV on early development. The results suggested HPV exposure was linked to two-cell embryo demise and delaying the exposure of HPV until later embryo stages permitted embryo development. HPV 16 was shown to decrease blastocyst formation while HPV 18 inhibited the blastocyst hatching process.

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“…In situ hybridization using HPV probes provides a rough estimate on the chromosomal localization, but does not allow ®ne mapping or even gathering sequence information (Cannizzaro et al, 1988;Mincheva et al, 1987). PCR techniques were used to amplify genomic areas containing integrated HPV sequences employing either ALU sequences (Carmody et al, 1996) or speci®c restriction sites (Thorland et al, 2000) as primer binding sites for the¯anking cellular sequences.…”

Section: Discussionmentioning

confidence: 99%

Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions

et al. 2002

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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 modi®cation of critical cellular sequences by integration of HPV genomes might signi®cantly 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 ampli®ed 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 ®ve cervical cancer cell lines. Database analyses of the cellular parts of these fusion transcripts revealed 51 dierent 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 identi®ed. 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.

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Regional chromosome localization of human papillomavirus intergration sites near fragile sites, oncogenes, and cancer chromosome breakpoints

Cited by 89 publications

References 7 publications

Viral integration sites in human papilloma virus-33-immortalized cervical keratinocyte cell lines

Viral integration sites in human papilloma virus-33-immortalized cervical keratinocyte cell lines

Human papilloma virus DNA exposure and embryo survival is stage-specific

Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions

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