Global DNA hypomethylation increases progressively in cervical dysplasia and carcinoma.
BACKGROUND
Global DNA hypomethylation has been observed in some human neoplasms and has been implicated as an important factor in carcinogenesis. The current study was designed to assess whether DNA hypomethylation occurs in cervical dysplasia and cancer, and to determine the relationship between the degree of DNA hypomethylation and the grade of neoplasia.


METHODS
Cervical biopsy specimens were obtained from colposcopically identifiable lesions in 41 patients with abnormal Pap smear results. The extent of global DNA methylation was assessed by incubating the extracted DNA with [3H]-S-adenosylmethionine and Sss1 methyltransferase, an enzyme that specifically catalyzes the transfer of methyl groups to cytosine residues in the cytosine-guanine doublet. The degree of exogenous 3H-methyl group incorporation into the DNA therefore is related reciprocally to the extent of endogenous DNA methylation. These data were compared with the histopathologic classification of the lesions.


RESULTS
The extent of 3H-methyl group incorporation was increased threefold and sevenfold in the DNA from cervical dysplasia and cancer, respectively, compared with the DNA from normal cervical tissue (P = 0.006, analysis of variance). Significant incremental increases in DNA hypomethylation were observed in the progression from normal and low grade squamous intraepithelial lesions (SIL) to high grade SIL and to cancer (P < 0.0001, trend).


CONCLUSIONS
These data show that global DNA hypomethylation is a significant epigenetic event in cervical carcinogenesis and that the degree of DNA hypomethylation increases with the grade of cervical neoplasia. These data suggest that global DNA methylation may serve as a biochemical marker of cervical neoplasia.
Vitamin Bioavailability Laboratory, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111.
Y I
YI
Kim
A
A
Giuliano
K D
KD
Hatch
A
A
Schneider
M A
MA
Nour
G E
GE
Dallal
J
J
Selhub
J B
JB
Mason
D002584:Cervix Uteri / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008745:Methylation; D002578:Uterine Cervical Dysplasia / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
D004247:DNA