Detection of hypermethylated genes in women with and without cervical neoplasia

Abstract

Background: DNA methylation changes are an early event in carcinogenesis and are often present in the precursor lesions of various cancers. We examined whether DNA methylation changes might be used as markers of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC). Methods: We used methylation-specific polymerase chain reaction (PCR) to analyze promoter hypermethylation of 20 genes, selected on the basis of their role in cervical cancer, in 319 exfoliated cell samples and matched tissue biopsy specimens collected during two studies of Senegalese women with increasingly severe CIN and ICC (histology negative/atypical squamous cells of undetermined significance [ASCUS] = 142, CIN-1 = 39, CIN-2 = 23, CIN-3/carcinoma in situ [CIS] = 23, ICC = 92). Logic regression was used to determine the best set of candidate genes to use as disease markers. All statistical tests were two-sided. Results: Similar promoter methylation patterns were seen in genes from exfoliated cell samples and corresponding biopsy specimens. For four genes (CDH13, DAPK1, RARB, and TWIST1), the frequency of hypermethylation increased statistically significantly with increasing severity of neoplasia present in the cervical biopsy (P