{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:56:50Z","timestamp":1791266210965,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2008,2,19]],"date-time":"2008-02-19T00:00:00Z","timestamp":1203379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Imprinted tumor suppressor genes may be particularly important in the pathogenesis of ovarian cancer. Two imprinted genes, paternally expressed 3 (<jats:italic>PEG3<\/jats:italic>) and aplasia Ras homologue member I (<jats:italic>ARHI<\/jats:italic>), are the most frequently down\u2010regulated in ovarian cancers on gene expression arrays.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p><jats:italic>PEG3<\/jats:italic> and <jats:italic>ARHI<\/jats:italic> expression levels were evaluated with real\u2010time reverse\u2010transcriptase polymerase chain reaction (PCR) analysis. Promoter methylation was measured by pyrosequencing, and loss of heterozygosity (LOH) was detected by PCR\u2010LOH assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p><jats:italic>PEG3<\/jats:italic> was down\u2010regulated in 75% and <jats:italic>ARHI<\/jats:italic> was down\u2010regulated in 88% of 40 ovarian cancers. <jats:italic>ARHI<\/jats:italic> CpG islands I and II were hypermethylated in 13 of 42 ovarian cancers (31%) and in 5 of 42 ovarian cancers (12%), respectively, and hypermethylation was associated with reduced <jats:italic>ARHI<\/jats:italic> expression in all 18 samples of ovarian cancer with CpG island hypermethylation. <jats:italic>PEG3<\/jats:italic> was hypermethylated in 11 of 42 ovarian cancers (26%), and <jats:italic>PEG3<\/jats:italic> expression was down\u2010regulated in 10 of those 11 cancers. LOH was detected in 8 of 35 informative cases for <jats:italic>ARHI<\/jats:italic> (23%) and in 5 of 25 informative cases for <jats:italic>PEG3<\/jats:italic> (20%). <jats:italic>PEG3<\/jats:italic> and <jats:italic>ARHI<\/jats:italic> expression was highly correlated in human ovarian cancers (correlation coefficient [R] = 0.69; <jats:italic>P<\/jats:italic> &lt; .0001). <jats:italic>PEG3<\/jats:italic> and <jats:italic>ARHI<\/jats:italic> also were methylated concordantly in ovarian cancers (R = 0.36; <jats:italic>P<\/jats:italic> = .019). Re\u2010expression of <jats:italic>PEG3<\/jats:italic>, similar to that of <jats:italic>ARHI<\/jats:italic>, markedly inhibited ovarian cancer growth. <jats:italic>ARHI<\/jats:italic> and <jats:italic>PEG3<\/jats:italic> expression could be restored by treatment with 5\u2010aza\u20102\u2032\u2010deoxycytidine and trichostatin A, consistent with the importance of promoter methylation and histone acetylation in regulating expression of both genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Loss of expression of the growth\u2010inhibitory imprinted genes <jats:italic>ARHI<\/jats:italic> and <jats:italic>PEG3<\/jats:italic> through promoter methylation, LOH, and other mechanisms may stimulate clonogenic growth and contribute to the pathogenesis of a majority of ovarian cancers. Cancer 2008. \u00a9 2008 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.23323","type":"journal-article","created":{"date-parts":[[2008,2,19]],"date-time":"2008-02-19T14:56:33Z","timestamp":1203432993000},"page":"1489-1502","source":"Crossref","is-referenced-by-count":149,"title":["Imprinted tumor suppressor genes <i>ARHI<\/i> and <i>PEG3<\/i> are the most frequently down\u2010regulated in human ovarian cancers by loss of heterozygosity and promoter methylation"],"prefix":"10.1002","volume":"112","author":[{"given":"Weiwei","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca 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