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bp(GOBP:"DNA methylation") -| r(HGNC:CCND2)
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Approximately 61,000 statements.
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Copyright (c) 2011-2012, Selventa. All rights reserved.
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BEL Framework Large Corpus Document
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PURPOSE: Loss or abnormal expression of Cyclin D2,a crucial cell cycle-regulatory gene, has been described in human cancers;however, data for prostate tumors are lacking. We investigated the epigeneticsilencing of Cyclin D2 gene in prostate cancers and correlated the data withclinicopathological features. EXPERIMENTAL DESIGN: Cyclin D2 promotermethylation was analyzed in 101 prostate cancer samples by methylation-specificPCR. In addition, we analyzed 32 nonmalignant prostate tissue samples, whichincluded 24 samples of benign disease, benign prostatic hypertrophy, orprostatitis and 7 normal tissues adjacent to cancer. The methylation status ofCyclin D2 was correlated with the methylation of nine other tumor suppressorgenes published previously from our laboratory on the same set of samples (R.Maruyama et al., Clin. Cancer Res., 8: 514-519, 2002). The methylation index wasdetermined as a reflection of the methylated fraction of the genes examined.RESULTS: The frequency of methylation of Cyclin D2 promoter was significantlyhigher in prostate cancers (32%) than in nonmalignant prostate tissues (6%; P =0.004), and it was not age related. Aberrant methylation was present atinsignificant levels in peripheral blood lymphocytes (8%). We also comparedmethylation of cyclin D2 with methylation of nine tumor suppressor genes[published previously from our laboratory (R. Maruyama et al., Clin. CancerRes., 8: 514-519, 2002)] studied in the same set of samples. The concordancesbetween methylation of Cyclin D2 and the methylation of RARbeta, GSTP1, CDH13,RASSF1A, and APC were statistically significant, whereas methylation of P16,DAPK, FHIT, and CDH1 were not significant. The differences in methylation indexbetween malignant and nonmalignant tissues for all 10 genes were statisticallysignificant (P < 0.0001). Among clinicopathological correlations, the highGleason score group had significantly greater methylation frequency of Cyclin D2(42%; P = 0.004). Although the high preoperative serum prostate-specific antigen(PSA) group did not have significantly greater methylation frequency,methylation of Cyclin D2 had higher mean PSA value. Also, the prostate cancersin the high Gleason score group had high mean values of PSA. CONCLUSIONS: Ourresults indicate that methylation of Cyclin D2 in prostate cancers correlateswith clinicopathological features of poor prognosis. These findings are ofbiological and potential clinical importance.
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Selventa
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