DNA methylation in serum and tumors of cervical cancer patients.
OBJECTIVE
Promoter hypermethylation has been recognized to play an important role in carcinogenesis. Numerous studies have demonstrated tumor-specific alterations, such as aberrant promoter hypermethylation, in DNA recovered from plasma or serum of patients with various malignancies. The aim of this study was to investigate the methylation status of various genes in cervical cancer patients and their association with clinicopathological characteristics and outcome of the disease.


METHODS
The methylation status of CALCA, hTERT, MYOD1, PGR (progesterone receptor), and TIMP3 was investigated in serum samples from 93 cervical cancer patients and 19 corresponding tissue samples using the MethyLight technique.


RESULTS
Aberrant promoter hypermethylation was detected in any of these genes in 87% (81 of 93) of the serum samples studied. Methylation of MYOD1 was detected more frequently in advanced stage. All of the genes found to be methylated in serum samples were also methylated in the corresponding tissue sample, except in one patient. Patients with unmethylated MYOD1 serum DNA had significantly better disease-free (P = 0.04) and overall survival (P = 0.02) in comparison with patients with methylated MYOD1.


CONCLUSIONS
To the best of our knowledge, this is, thus far, the largest study investigating aberrant promoter hypermethylation in serum samples from cancer patients and the first study investigating methylation patterns in sera of cervical cancer patients. Our results suggest that serological detection of MYOD1 promoter hypermethylation may be of potential use as a prognostic marker for discriminating cervical cancer patients at high risk for lymph node metastasis or relapse. Additional studies, including a panel of additional genes, are necessary to elucidate the role of aberrant methylation in serum as a tool for surveillance of cervical cancer.
Widschwendter
Andreas
A
Department of Obstetrics and Gynecology, Innsbruck University Hospital, Innsbruck, Austria.
Müller
Hannes M
HM
Fiegl
Heidi
H
Ivarsson
Lennart
L
Wiedemair
Annemarie
A
Müller-Holzner
Elisabeth
E
Goebel
Georg
G
Marth
Christian
C
Widschwendter
Martin
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002116:Calcitonin / Q000235:genetics; D015740:Calcitonin Gene-Related Peptide; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000097:blood* / Q000235:genetics*
C000606589:CALCA protein, human; D004268:DNA-Binding Proteins; D011498:Protein Precursors; D011980:Receptors, Progesterone; D002116:Calcitonin; D004247:DNA; D019098:Telomerase; D015740:Calcitonin Gene-Related Peptide