Human papillomavirus type 16 E6 variants in cervical carcinoma: relationship to host genetic factors and clinical parameters.

2.50
Hdl Handle:
http://hdl.handle.net/10541/90788
Title:
Human papillomavirus type 16 E6 variants in cervical carcinoma: relationship to host genetic factors and clinical parameters.
Authors:
Brady, Claire S; Duggan-Keen, Margaret F; Davidson, Judith A; Varley, Jennifer; Stern, Peter L
Abstract:
Infection with human papillomavirus type 16 (HPV-16) confers a high risk for the development of cervical neoplasia. Variants of this virus may interact differentially with host genetic factors, possibly altering the disease course. Thus, HPV-16 E6 variants may differ in their ability to degrade p53 whereas the polymorphic p53 alleles may provide more or less susceptible substrates for the viral oncogene product. Also, E6 variants may differ in immunogenicity by generating different peptides for presentation by polymorphic HLA molecules to specific T cells. This study examines HPV-16 E6 sequence variation in cervical carcinomas from the UK and its relationship to polymorphism of HLA and p53 and to clinical parameters. Sequence analysis of the HPV-16 E6 ORF from 77 tumour biopsies detected the viral prototype sequence in 38% of cases. The most common variation detected was a T to G transition at base pair 350, resulting in an amino acid change from a leucine to a valine. Overall, the frequencies of 350T and 350G sequences were similar (49. 4% and 50.6% respectively). Other mutations of lower frequencies were detected together with and independently of 350G. HPV-16 E6 sequence variation at base pair 350 did not correlate with HLA genotype or clinical outcome. There was no difference in the distribution of p53 proline and arginine alleles between HPV-16-positive cervical carcinoma patients and local controls, and no influence on clinical outcome; however, there was a trend for an increased frequency of p53 arginine homozygotes among the 350T carcinoma patients.
Affiliation:
Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
Citation:
Human papillomavirus type 16 E6 variants in cervical carcinoma: relationship to host genetic factors and clinical parameters. 1999, 80 ( Pt 12):3233-40 J. Gen. Virol.
Journal:
Journal of General Virology
Issue Date:
Dec-1999
URI:
http://hdl.handle.net/10541/90788
PubMed ID:
10567656
Type:
Article
Language:
en
ISSN:
0022-1317
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBrady, Claire Sen
dc.contributor.authorDuggan-Keen, Margaret Fen
dc.contributor.authorDavidson, Judith Aen
dc.contributor.authorVarley, Jenniferen
dc.contributor.authorStern, Peter Len
dc.date.accessioned2010-01-28T10:52:51Z-
dc.date.available2010-01-28T10:52:51Z-
dc.date.issued1999-12-
dc.identifier.citationHuman papillomavirus type 16 E6 variants in cervical carcinoma: relationship to host genetic factors and clinical parameters. 1999, 80 ( Pt 12):3233-40 J. Gen. Virol.en
dc.identifier.issn0022-1317-
dc.identifier.pmid10567656-
dc.identifier.urihttp://hdl.handle.net/10541/90788-
dc.description.abstractInfection with human papillomavirus type 16 (HPV-16) confers a high risk for the development of cervical neoplasia. Variants of this virus may interact differentially with host genetic factors, possibly altering the disease course. Thus, HPV-16 E6 variants may differ in their ability to degrade p53 whereas the polymorphic p53 alleles may provide more or less susceptible substrates for the viral oncogene product. Also, E6 variants may differ in immunogenicity by generating different peptides for presentation by polymorphic HLA molecules to specific T cells. This study examines HPV-16 E6 sequence variation in cervical carcinomas from the UK and its relationship to polymorphism of HLA and p53 and to clinical parameters. Sequence analysis of the HPV-16 E6 ORF from 77 tumour biopsies detected the viral prototype sequence in 38% of cases. The most common variation detected was a T to G transition at base pair 350, resulting in an amino acid change from a leucine to a valine. Overall, the frequencies of 350T and 350G sequences were similar (49. 4% and 50.6% respectively). Other mutations of lower frequencies were detected together with and independently of 350G. HPV-16 E6 sequence variation at base pair 350 did not correlate with HLA genotype or clinical outcome. There was no difference in the distribution of p53 proline and arginine alleles between HPV-16-positive cervical carcinoma patients and local controls, and no influence on clinical outcome; however, there was a trend for an increased frequency of p53 arginine homozygotes among the 350T carcinoma patients.en
dc.language.isoenen
dc.subjectCancer Stagingen
dc.subjectTumour Virus Infectionsen
dc.subjectUterine Cervical Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshFemale-
dc.subject.meshGenes, MHC Class I-
dc.subject.meshGenes, MHC Class II-
dc.subject.meshGenes, p53-
dc.subject.meshGenetic Variation-
dc.subject.meshHumans-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Staging-
dc.subject.meshOncogene Proteins, Viral-
dc.subject.meshPapillomaviridae-
dc.subject.meshPapillomavirus Infections-
dc.subject.meshPoint Mutation-
dc.subject.meshPolymerase Chain Reaction-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshRepressor Proteins-
dc.subject.meshSequence Analysis, DNA-
dc.subject.meshTumor Virus Infections-
dc.subject.meshUterine Cervical Neoplasms-
dc.titleHuman papillomavirus type 16 E6 variants in cervical carcinoma: relationship to host genetic factors and clinical parameters.en
dc.typeArticleen
dc.contributor.departmentDepartment of Immunology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.en
dc.identifier.journalJournal of General Virologyen

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