Register for email alerts and news feeds:
This journal | BMJ Group
rss
Molecular Pathology 2000;53:201-206; doi:10.1136/mp.53.4.201
Copyright © 2000 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists.
J Clin Pathol: Mol Pathol 2000; 53:201-206
© 2000 Journal of Clinical Pathology

HPV-16 E2 gene disruption and sequence variation in CIN 3 lesions and invasive squamous cell carcinomas of the cervix: relation to numerical chromosome abnormalities

D A Graham1 and C S Herrington1

1 Department of Pathology, University of Liverpool, Royal Liverpool University Hospital, Daulby Street, Liverpool L69 3GA, UK

Correspondence to:
Professor Herrington email: c.s.herrington{at}liv.ac.uk

Aim—To test the hypothesis that, because the human papillomavirus (HPV) E2 protein represses viral early gene transcription, E2 gene sequence variation or disruption could play a part in the induction of the numerical chromosome abnormalities that have been described in squamous cervical lesions.

Methods—The integrity and sequence of the E2 gene from 11 cervical intraepithelial neoplasia (CIN) grade 3 lesions and 14 invasive squamous cell carcinomas, all of which contained HPV-16, were analysed by the polymerase chain reaction (PCR). The E2 gene was amplified in three overlapping fragments and PCR products sequenced directly. Chromosome abnormalities were identified by interphase cytogenetics using chromosome specific probes for chromosomes 1, 3, 11, 17, 18, and X.

Results—E2 gene disruption was present in significantly more invasive carcinomas (eight of 14) than CIN 3 lesions (one of 11) (p = 0.03). No association was found between E2 disruption and the presence of a numerical chromosome abnormality. The E2 gene from the non-disrupted isolates was sequenced and wild-type (n = 5) and variant (n = 11) sequences identified. Variant sequences belonged to European and African classes and contained from one to 15 amino acid substitutions. Although numerical chromosome abnormalities were significantly more frequent in invasive squamous cell carcinoma than CIN 3 (p = 0.04), there was no significant relation between the presence of sequence variation and either histological diagnosis or chromosome abnormality.

Conclusions—These data do not support the hypothesis that E2 gene disruption or variation is important in the induction of chromosome imbalance in these lesions. However, there is a relation between E2 gene disruption and the presence of invasive disease.

Key Words: papillomavirus • E2 gene • cervix • chromosome


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

This article has been cited by other articles:

  • Collins, S. I., Constandinou-Williams, C., Wen, K., Young, L. S., Roberts, S., Murray, P. G., Woodman, C. B.J. (2009). Disruption of the E2 Gene Is a Common and Early Event in the Natural History of Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study. Cancer Res. 69: 3828-3832 [Abstract] [Full Text]  
  • Azizi, N., Brazete, J., Hankins, C., Money, D., Fontaine, J., Koushik, A., Rachlis, A., Pourreaux, K., Ferenczy, A., Franco, E., Francois Coutlee for The Canadian Women's HIV Stud, (2008). Influence of human papillomavirus type 16 (HPV-16) E2 polymorphism on quantification of HPV-16 episomal and integrated DNA in cervicovaginal lavages from women with cervical intraepithelial neoplasia. J. Gen. Virol. 89: 1716-1728 [Abstract] [Full Text]  
  • Arias-Pulido, H., Peyton, C. L., Joste, N. E., Vargas, H., Wheeler, C. M. (2006). Human papillomavirus type 16 integration in cervical carcinoma in situ and in invasive cervical cancer.. J. Clin. Microbiol. 44: 1755-1762 [Abstract] [Full Text]  
  • Davidson, E. J., Sehr, P., Faulkner, R. L., Parish, J. L., Gaston, K., Moore, R. A., Pawlita, M., Kitchener, H. C., Stern, P. L. (2003). Human papillomavirus type 16 E2- and L1-specific serological and T-cell responses in women with vulval intraepithelial neoplasia. J. Gen. Virol. 84: 2089-2097 [Abstract] [Full Text]  

Pathology jobs

Pathology jobs