Open AccessPromoter methylation status of the Cyclin D2 gene is associated with poor prognosis in human epithelial ovarian cancer
Author(s) -
Sakuma Michiko,
Akahira Junichi,
Ito Kiyoshi,
Niikura Hitoshi,
Moriya Takuya,
Okamura Kunihiro,
Sasano Hironobu,
Yaegashi Nobuo
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00394.x
Subject(s) - methylation , cancer research , dna methylation , biology , cyclin d2 , cyclin d1 , microbiology and biotechnology , cyclin b , cancer , cell cycle , gene expression , gene , genetics
Gene silencing associated with aberrant DNA methylation of promoter CpG islands is one mechanism through which several genes may be inactivated in human cancers. Cyclin D2, a member of the D‐type cyclins, implicated in cell cycle regulation, differentiation and malignant transformation, is inactivated due to aberrant DNA methylation in several human cancers. In the present study, we examined the promoter methylation status and expression of Cyclin D2 in human epithelial ovarian cancer, and then determined the relationship between methylation status and various clinicopathological variables. Twelve ovarian cancer cell lines and 71 surgical specimens were examined by methylation‐specific polymerase chain reaction and quantitative reverse transcription–polymerase chain reaction to evaluate the methylation status and expression of the Cyclin D2 gene. The relationship between methylation status and various clinicopathological variables was evaluated using statistical analysis. Aberrant methylation of Cyclin D2 was present in five of 12 ovarian cancer cell lines and 16 of 71 primary ovarian cancer tissues. In five cell lines with methylation, expression of the Cyclin D2 gene tended to be lower than in cell lines without methylation. In ovarian cancer tissues, methylation bands were detected in 16 of 71 cases. The methylation status of Cyclin D2 was associated with advanced stage and a residual tumor size (>2 cm) ( P = 0.027 and P = 0.031, respectively). Based on univariate analysis, patients with aberrant methylation of the Cyclin D2 promoter had a significantly worse chance of disease‐free survival than those without methylation ( P = 0.021). Our results suggest that aberrant promoter methylation of the Cyclin D2 gene is significantly associated with patient prognosis in epithelial ovarian cancer. ( Cancer Sci 2007; 98: 380 –386)