Viral integration and fragile sites in human papillomavirus‐lmmortalized human keratinocyte cell lines

Smith, Patricia P.; Friedman, Cynthia; Bryant, Eileen; McDougall, James K.

doi:10.1002/gcc.2870050209

Cited by 88 publications

(66 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There was a high correlation between the individual locations of HPV integration sites and fragile sites in the genome since 40 of 57 mapped HPV integration sites were found near fragile sites. These observations con®rm data of other investigators, who have reported HPV integration sites near fragile sites in various cell lines and very few cervical carcinoma samples (Popescu et al, 1987;Smith et al, 1992;Thorland et al, 2000).…”

Section: Discussionsupporting

confidence: 91%

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

et al. 2002

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 91%

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

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Smith et al (1992) reported that HPV integration sites were consistent with integration near or within known fragile sites in ®ve of six HPVimmortalized keratinocyte cell lines. Wilke et al (1996) have shown that a region of frequent breakage within FRA3B coincided with a previously characterized site of HPV16 integration in a primary cervical carcinoma.…”

Section: Discussionmentioning

confidence: 85%

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact

et al. 1998

View full text Add to dashboard Cite

FRA3B at human chromosomal band 3p14.2 is the most active common fragile site in the human genome. The molecular mechanism of fragility at this region remains unknown but does not involve expansion of a trinucleotide or minisatellite repeat as has been observed for several of the cloned rare fragile sites. Deletions and rearrangements at FRA3B have been observed in a number of distinct tumors. The recently identi®ed putative tumor suppressor gene FHIT spans FRA3B, and various groups have reported identifying deletions in this gene in dierent tumors. Using a high density of PCR ampli®able markers within FRA3B searching for deletions in the FRA3B region, we have analysed 21 tumor cell lines derived from renal cell, pancreatic, and ovarian carcinomas. We found a commonly deleted region in the renal cell and ovarian carcinoma cell lines located in the middle of an HPV16 viral integration site. Despite the presence of deletions in the FRA3B region in most of the cell lines, we did not detect alterations in FHIT exons in any of the cell lines examined. Thus, deletions of 3p14.2 in these carcinoma cell lines may simply re¯ect instability of the FRA3B region during tumor progression.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Viral integration and fragile sites in human papillomavirus‐lmmortalized human keratinocyte cell lines

Cited by 88 publications

References 34 publications

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

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

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact

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

Contact Info

Product

Resources

About