Detection of hypermethylated genes in tumor and plasma of cervical cancer patients

Objective. The aim of this study is to investigate the prevalence of promotor CpG island methylation of the death-associated protein kinase (DAPK), p16, and O-6-methylguanine-DNA methyltransferase (MGMT) genes in both tumor and plasma samples of cervical cancers. Methods. Methylation-specific PCR (MSP) was employed to detect promotor CpG island methylation of the DAPK, p16, and MGMT genes in 85 surgical tumor tissue samples and 40 pretreatment plasma samples from cervical cancers. Results. Promotor CpG island methylation of DAPK, p16, and MGMT was detectable, respectively, in 60%, 28.2%, and 18.8% of cases of cervical tumor DNA; and in 40%, 10%, and 75% of cases of patients' plasma DNA. Moreover, at least one of the three methylated genes was detected in 75.3% (64/85) of cases of tumor and in 55% (22/40) of cases of plasma. Higher prevalence of methylation of DAPK was found in squamous cell carcinoma than in adenocarcinoma in both univariate and multivariate analysis. Methylation of p16 was significantly associated with that of MGMT in both univariate and multivariate analysis. The methylation pattern in primary tumor and plasma was found to be concordant in 23 patients with matched tissue and plasma samples. In cases positive for DAPK and p16 methylation in tumor, detection in the paired plasma sample was 64.3% (9/14) and 33.3% (3/9), respectively. Conclusions. Promotor CpG island methylation is a frequent event in cervical carcinogenesis. Detection of the methylated sequences in the circulation suggests that plasma DNA methylation warrants further study to determine its potential role in cancer management. (C) 2004 Elsevier Inc. All rights reserved.