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 7.5% 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.
Yang
H J
HJ
Department of Obstetrics and Gynaecology, Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.
Liu
V W S
VW
Wang
Y
Y
Chan
K Y K
KY
Tsang
P C K
PC
Khoo
U S
US
Cheung
A N Y
AN
Ngan
H Y S
HY
D000328:Adult; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood*; D064550:Death-Associated Protein Kinases; D005260:Female; D019942:Genes, p16; D006801:Humans; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011401:Promoter Regions, Genetic; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D004273:DNA, Neoplasm; D019853:O(6)-Methylguanine-DNA Methyltransferase; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases