Single copy heterozygote integration of HPV 33 in chromosomal band 5p14 is found in an epithelial cell clone with selective growth advantage

Peitsaro, Panu; Hietanen, Sakari; Johansson, Bo; Lakkala, Taina; Syrjänen, Stina

doi:10.1093/carcin/23.6.1057

Cited by 25 publications

(24 citation statements)

References 50 publications

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“…58 However, at passages 18-20 onward, only the integrated form was detected. 58 After identifying the exact integration site of HPV-33 at chromosome 5p14, we were able to trace the 51 Ringström ( presence of the integrated form of HPV-33 at early passages and even in the original biopsy. However, the copy numbers of the integrated form of HPV-33 were very low.…”

Section: Physical State Of Hpv In Tonsillar Carcinomasmentioning

confidence: 98%

HPV infections and tonsillar carcinoma

2004

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Since human papillomavirus (HPV) was first linked to laryngeal/oral carcinomas in 1983, several studies have confirmed its causal role in a subgroup of upper aerodigestive tract tumours. Of the non-genital cancers, tonsillar carcinomas (TCs) have the strongest association with HPV. By the end of 2002, 432 TCs had been analysed for HPV DNA. Overall detection rate was 51%, with HPV-16 being the most prevalent (84%). The original proposal that HPV-33 would be the most frequent HPV in TCs has not been confirmed, being present in only 4.6% of cases. HPV copy numbers are similar to those found in genital carcinomas (10–300 copies/cell), although HPV is mainly episomal in TC. The importance of this observation is unclear, although a role for subepithelial proliferative lymphatic tissue has been speculated. Patients with HPV-16 positive tumours have better overall and disease specific survival than HPV negative patients. They are also younger and the association with conventional risk factors—smoking and drinking—is less significant than in HPV negative patients. Thus, recent data suggest a distinct pattern for HPV-16 positive TCs.

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Section: Physical State Of Hpv In Tonsillar Carcinomasmentioning

confidence: 98%

HPV infections and tonsillar carcinoma

2004

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“…The viral integration site has been scored using the amplification of papillomavirus oncogene transcripts assay (19). The cell line is widely characterized also later (20)(21)(22)26 …”

Section: Cell Linesmentioning

confidence: 99%

“…We have used the HPV33-positive UT-DEC-1 cell line (originally established from VAIN1, vaginal intraepithelial lesion) as a model for HPV-induced carcinogenesis in vitro, and our previous studies have revealed the following critical features: (a) the HPV genome is mostly episomal in cells until passages 19 and 20, during which the episomes are totally lost by integration; (b) in the subsequent passages, only the integrated form of HPV is detected at the chromosome 5p14 integration site (19); (c) in the UT-DEC-1 tissue culture model, progressive changes in the phenotype of the epithelium are found (20); (d) the cell line loses its response to retinoids at later passages (21); and (e) a shift from the mitogen-activated protein kinase pathway to cell cycle dysregulation (G 2 -M) is found. Taken together, these results support the progression toward malignancy (22).…”

Section: Introductionmentioning

confidence: 99%

Molecular Markers Implicating Early Malignant Events in Cervical Carcinogenesis

Koskimaa

Kurvinen

Costa

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Human papillomavirus can induce a stepwise progression of precursor lesions to carcinoma. Sensitive and specific molecular markers are needed to identify the cervical lesions (CIN) at risk for this progression. hTERT activation could be one indicator of a point of no return in malignant progression.Methods: The UT-DEC-1 cell line is an in vitro model for the study of human papillomavirus-induced progression. Using molecular mining, nine potential genes interlinking hTERT and viral oncogene expression with the phenotypical features of CIN2 were identified. After preliminary testing with real-time PCR, five genes were selected for further analysis: hTERT, DKC1, Bcl-2, S100A8, and S100A9. These proteins were also tested in a series of 120 CIN lesions using immunohistochemistry.Results: Analysis of the mRNA expression of these genes at different cell passages revealed three time points with significant changes. hTERT, Bcl-2, and S100A9 were also overexpressed in CIN lesions, and the expression pattern changed during the progression toward CIN3 lesions.Conclusions: These identified time points that were combined with the mRNA overexpression of target genes matched events previously shown to be important in the progression toward malignancy: (a) the viral integration into the cell genome and episome loss; (b) the selection of cells with an acquired growth advantage and ability to maintain telomerase activity; and (c) the final stage of malignancy with permanently upregulated telomerase.Impact: hTERT, Bcl-2, and S100A9 together might compose a potential prognostic marker panel for the assessment of CIN lesions. These results, however, need further validation in prospective clinical settings.

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“…HPV can either replicate independently as episomes or by integrating into the host DNA. The integration of high-risk type HPV DNA is probably the most crucial event for tumorigenesis (Peitsaro et al, 2002). This heterogeneous group of viruses has the ability to infect and replicate in squamous epithelia of both keratinised and mucosal surfaces.…”

Section: Hpv and Cervical Cancermentioning

confidence: 99%