title: Inactivation of the p16INK4A gene by methylation is not a frequent event in sporadic ovarian carcinoma.
abstract: The p16INK4A tumour suppressor gene (p16) encodes for a cyclin-dependant kinase inhibitor which plays a role in the phosphorylation of the retinoblastoma protein (pRb) during regulation of the G1-S phase of the cell cycle. Loss of heterozygosity at 9p21, the chromosomal location of the p16 gene, has been reported in a broad range of tumours and this is usually indicative of the presence of a tumour suppressor gene, the second allele being frequently inactivated by mutation or deletion. The p16 gene, however, is often found not be mutated or deleted and it has been suggested that hypermethylation of the CpG islands of the gene may be an alternative mechanism of gene inactivation. We sought to determine the levels of p16 abnormality in a series of epithelial ovarian carcinomas in an attempt to clarify the presently conflicting evidence of whether or not hypermethylation of the p16 gene plays a role in ovarian carcinogenesis. We analysed 57 primary ovarian tumours and their corresponding blood DNA using SSCP analysis, sequencing and the methylation specific PCR (MSP) technique. We found low levels of mutation (6.7% of malignant tumours) and no evidence of methylation in any of our samples, suggesting that neither mutation or hypermethylation of the CpG islands of the p16 gene play an important role in ovarian carcinogenesis.
authors.affiliation: Department of Medical Genetics, Medical School Building, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK. i.brown@abdn.ac.uk
authors.forename: I
authors.initials: I
authors.lastname: Brown
authors.forename: B J
authors.initials: BJ
authors.lastname: Milner
authors.forename: P H
authors.initials: PH
authors.lastname: Rooney
authors.forename: N E
authors.initials: NE
authors.lastname: Haites
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005784:Gene Amplification; D019942:Genes, p16; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA