Abstract
Human papillomavirus (HPV) infection appears to be an early event in cervical carcinogenesis with additional abnormalities being required for biological transformation. We have analysed 179 low-grade cervical squamous intra-epithelial lesions (SILs) and 15 normal cervices for the presence of HPV using both in situ hybridization and polymerase chain reaction (PCR). PCR was performed with GP5+/GP6+ primers followed by hybridization using probes for low (HPV 6, 11, 40, 42, 43, 44), intermediate (HPV 31, 33, 35, 39, 51, 52, 58, 59, 66 and 68) and high-risk HPVs (HPV 16, 18, 45 and 56). Interphase cytogenetic analysis using pericentromeric probes for chromosomes 1, 3, 4, 6, 10, 11, 17, 18 and X was also performed to identify numerical chromosomal abnormalities. Tetrasomy of all nine chromosomes was identified within basal keratinocytes, was restricted to epithelia infected with high risk (17 of 46) or intermediate risk (23 of 83) HPVs but was not HPV type-specific. Tetrasomy was not identified in any of the epithelia infected with low risk HPVs (n = 62). These numbers include multiple infection. These findings indicate that the induction of tetrasomy is a property restricted to high and intermediate-risk HPV types but that it is not type-specific. The factors governing which lesions will develop this abnormality are as yet unclear. © 2000 Cancer Research Campaign
Keywords: cervix, human papillomavirus, keratinocyte, chromosome
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- Arends M. J., Wyllie A. H., Bird C. C. Papillomaviruses and human cancer. Hum Pathol. 1990 Jul;21(7):686–698. doi: 10.1016/0046-8177(90)90027-3. [DOI] [PubMed] [Google Scholar]
- Atkin N. B. Cytogenetics of carcinoma of the cervix uteri: a review. Cancer Genet Cytogenet. 1997 May;95(1):33–39. doi: 10.1016/s0165-4608(97)83452-8. [DOI] [PubMed] [Google Scholar]
- Di Leonardo A., Khan S. H., Linke S. P., Greco V., Seidita G., Wahl G. M. DNA rereplication in the presence of mitotic spindle inhibitors in human and mouse fibroblasts lacking either p53 or pRb function. Cancer Res. 1997 Mar 15;57(6):1013–1019. [PubMed] [Google Scholar]
- Frattini M. G., Lim H. B., Doorbar J., Laimins L. A. Induction of human papillomavirus type 18 late gene expression and genomic amplification in organotypic cultures from transfected DNA templates. J Virol. 1997 Sep;71(9):7068–7072. doi: 10.1128/jvi.71.9.7068-7072.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fukasawa K., Choi T., Kuriyama R., Rulong S., Vande Woude G. F. Abnormal centrosome amplification in the absence of p53. Science. 1996 Mar 22;271(5256):1744–1747. doi: 10.1126/science.271.5256.1744. [DOI] [PubMed] [Google Scholar]
- Galloway D. A., McDougall J. K. The disruption of cell cycle checkpoints by papillomavirus oncoproteins contributes to anogenital neoplasia. Semin Cancer Biol. 1996 Dec;7(6):309–315. doi: 10.1006/scbi.1996.0040. [DOI] [PubMed] [Google Scholar]
- Hashida T., Yasumoto S. Induction of chromosome abnormalities in mouse and human epidermal keratinocytes by the human papillomavirus type 16 E7 oncogene. J Gen Virol. 1991 Jul;72(Pt 7):1569–1577. doi: 10.1099/0022-1317-72-7-1569. [DOI] [PubMed] [Google Scholar]
- Herrington C. S. Human papillomaviruses and cervical neoplasia. II. Interaction of HPV with other factors. J Clin Pathol. 1995 Jan;48(1):1–6. doi: 10.1136/jcp.48.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Higgins G. D., Uzelin D. M., Phillips G. E., McEvoy P., Marin R., Burrell C. J. Transcription patterns of human papillomavirus type 16 in genital intraepithelial neoplasia: evidence for promoter usage within the E7 open reading frame during epithelial differentiation. J Gen Virol. 1992 Aug;73(Pt 8):2047–2057. doi: 10.1099/0022-1317-73-8-2047. [DOI] [PubMed] [Google Scholar]
- Jacobs M. V., de Roda Husman A. M., van den Brule A. J., Snijders P. J., Meijer C. J., Walboomers J. M. Group-specific differentiation between high- and low-risk human papillomavirus genotypes by general primer-mediated PCR and two cocktails of oligonucleotide probes. J Clin Microbiol. 1995 Apr;33(4):901–905. doi: 10.1128/jcm.33.4.901-905.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lorincz A. T., Reid R., Jenson A. B., Greenberg M. D., Lancaster W., Kurman R. J. Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types. Obstet Gynecol. 1992 Mar;79(3):328–337. doi: 10.1097/00006250-199203000-00002. [DOI] [PubMed] [Google Scholar]
- Nilsson C. H., Bakos E., Petry K. U., Schneider A., Dürst M. Promoter usage in the E7 ORF of HPV16 correlates with epithelial differentiation and is largely confined to low-grade genital neoplasia. Int J Cancer. 1996 Jan 3;65(1):6–12. doi: 10.1002/(SICI)1097-0215(19960103)65:1<6::AID-IJC2>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
- Remmink A. J., Walboomers J. M., Helmerhorst T. J., Voorhorst F. J., Rozendaal L., Risse E. K., Meijer C. J., Kenemans P. The presence of persistent high-risk HPV genotypes in dysplastic cervical lesions is associated with progressive disease: natural history up to 36 months. Int J Cancer. 1995 May 4;61(3):306–311. doi: 10.1002/ijc.2910610305. [DOI] [PubMed] [Google Scholar]
- Slebos R. J., Lee M. H., Plunkett B. S., Kessis T. D., Williams B. O., Jacks T., Hedrick L., Kastan M. B., Cho K. R. p53-dependent G1 arrest involves pRB-related proteins and is disrupted by the human papillomavirus 16 E7 oncoprotein. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5320–5324. doi: 10.1073/pnas.91.12.5320. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Solinas-Toldo S., Dürst M., Lichter P. Specific chromosomal imbalances in human papillomavirus-transfected cells during progression toward immortality. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3854–3859. doi: 10.1073/pnas.94.8.3854. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Southern S. A., Evans M. F., Herrington C. S. Basal cell tetrasomy in low-grade cervical squamous intraepithelial lesions infected with high-risk human papillomaviruses. Cancer Res. 1997 Oct 1;57(19):4210–4213. [PubMed] [Google Scholar]
- Southern S. A., Herrington C. S. Assessment of intra-tumoral karyotypic heterogeneity by interphase cytogenetics in paraffin wax sections. Clin Mol Pathol. 1996 Oct;49(5):M283–M289. doi: 10.1136/mp.49.5.m283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Southern S. A., Herrington C. S. Interphase karyotypic analysis of chromosomes 11, 17 and X in invasive squamous-cell carcinoma of the cervix: morphological correlation with HPV infection. Int J Cancer. 1997 Mar 4;70(5):502–507. doi: 10.1002/(sici)1097-0215(19970304)70:5<502::aid-ijc2>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
- Steenbergen R. D., Walboomers J. M., Meijer C. J., van der Raaij-Helmer E. M., Parker J. N., Chow L. T., Broker T. R., Snijders P. J. Transition of human papillomavirus type 16 and 18 transfected human foreskin keratinocytes towards immortality: activation of telomerase and allele losses at 3p, 10p, 11q and/or 18q. Oncogene. 1996 Sep 19;13(6):1249–1257. [PubMed] [Google Scholar]
- Steinmann K. E., Pei X. F., Stöppler H., Schlegel R., Schlegel R. Elevated expression and activity of mitotic regulatory proteins in human papillomavirus-immortalized keratinocytes. Oncogene. 1994 Feb;9(2):387–394. [PubMed] [Google Scholar]
- Stewart Z. A., Leach S. D., Pietenpol J. A. p21(Waf1/Cip1) inhibition of cyclin E/Cdk2 activity prevents endoreduplication after mitotic spindle disruption. Mol Cell Biol. 1999 Jan;19(1):205–215. doi: 10.1128/mcb.19.1.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas J. T., Laimins L. A. Human papillomavirus oncoproteins E6 and E7 independently abrogate the mitotic spindle checkpoint. J Virol. 1998 Feb;72(2):1131–1137. doi: 10.1128/jvi.72.2.1131-1137.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White A. E., Livanos E. M., Tlsty T. D. Differential disruption of genomic integrity and cell cycle regulation in normal human fibroblasts by the HPV oncoproteins. Genes Dev. 1994 Mar 15;8(6):666–677. doi: 10.1101/gad.8.6.666. [DOI] [PubMed] [Google Scholar]
- Xiong Y., Kuppuswamy D., Li Y., Livanos E. M., Hixon M., White A., Beach D., Tlsty T. D. Alteration of cell cycle kinase complexes in human papillomavirus E6- and E7-expressing fibroblasts precedes neoplastic transformation. J Virol. 1996 Feb;70(2):999–1008. doi: 10.1128/jvi.70.2.999-1008.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]