Genetic characterization of the human papillomavirus (HPV) 18 E2 gene in clinical specimens suggests the presence of a subtype with decreased oncogenic potential
✍ Scribed by Julia L. Hecht; Anna S. Kadish; Gang Jiang; Robert D. Burk
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- French
- Weight
- 991 KB
- Volume
- 60
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
HPV 18 is associated with 2 divergent phenotypes: (i) aggressive cervical cancer and a preponderance of cancer relative to cervical intra-epithelial neoplasia (CIN) and (ii) benign warty lesions of the cervix. The €2 gene of HPV 18 encodes a regulatory protein that represses viral oncogene transcription and is involved in viral replication. Variation within the €2 gene of HPV 18 and its correlation with the morphologic grade of associated lesions were analyzed in a sample of 20 HPV I &positive cervical specimens representing a spectrum of pathology from low-grade CIN to cervical cancer. An amplifiable HPV 18 €2 gene was present in 3 of 5 cancers, indicating that E2 disruption was not required for cancer development. Single-strand conformation polymorphism and PCR analyses revealed a high degree of polymorphism throughout the €2 gene. Direct DNA sequencing of both strands of a 154-bp fragment revealed a variability of 5.8%. Six intra-epithelial lesions contained alterations in common that account for 3.9% of the variation and appear to constitute a subtype. Within the 154-bp region, 2 of 3 cervical cancers and 0 of I 2 intra-epithelial lesions were identical to the published HPV 18 sequence. DNA sequence analysis of a region extending into the €5 open reading frame revealed deletions in the E2/€5 intragenic region that were present in 50% of the members of the subtype. Our data demonstrate significant sequence variation within the €2 gene and suggest the presence of an HPV 18 subtype with decreased oncogenic potential.