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http://purl.uniprot.org/citations/18286529http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18286529http://www.w3.org/2000/01/rdf-schema#comment"

Background

Imprinted tumor suppressor genes may be particularly important in the pathogenesis of ovarian cancer. Two imprinted genes, paternally expressed 3 (PEG3) and aplasia Ras homologue member I (ARHI), are the most frequently down-regulated in ovarian cancers on gene expression arrays.

Methods

PEG3 and ARHI expression levels were evaluated with real-time reverse-transcriptase polymerase chain reaction (PCR) analysis. Promoter methylation was measured by pyrosequencing, and loss of heterozygosity (LOH) was detected by PCR-LOH assays.

Results

PEG3 was down-regulated in 75% and ARHI was down-regulated in 88% of 40 ovarian cancers. ARHI 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 ARHI expression in all 18 samples of ovarian cancer with CpG island hypermethylation. PEG3 was hypermethylated in 11 of 42 ovarian cancers (26%), and PEG3 expression was down-regulated in 10 of those 11 cancers. LOH was detected in 8 of 35 informative cases for ARHI (23%) and in 5 of 25 informative cases for PEG3 (20%). PEG3 and ARHI expression was highly correlated in human ovarian cancers (correlation coefficient [R]=0.69; P< .0001). PEG3 and ARHI also were methylated concordantly in ovarian cancers (R=0.36; P= .019). Re-expression of PEG3, similar to that of ARHI, markedly inhibited ovarian cancer growth. ARHI and PEG3 expression could be restored by treatment with 5-aza-2'-deoxycytidine and trichostatin A, consistent with the importance of promoter methylation and histone acetylation in regulating expression of both genes.

Conclusions

Loss of expression of the growth-inhibitory imprinted genes ARHI and PEG3 through promoter methylation, LOH, and other mechanisms may stimulate clonogenic growth and contribute to the pathogenesis of a majority of ovarian cancers."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.org/dc/terms/identifier"doi:10.1002/cncr.23323"xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/author"Lu Z."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/author"Yu Y."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/author"Feng W."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/author"Lu K.H."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/author"Bast R.C. Jr."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/author"Issa J.P."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/author"Fishman D.M."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/author"Marquez R.T."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/name"Cancer"xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/pages"1489-1502"xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/title"Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation."xsd:string
http://purl.uniprot.org/citations/18286529http://purl.uniprot.org/core/volume"112"xsd:string
http://purl.uniprot.org/citations/18286529http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18286529
http://purl.uniprot.org/citations/18286529http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18286529
http://purl.uniprot.org/uniprot/#_O95661-mappedCitation-18286529http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18286529
http://purl.uniprot.org/uniprot/O95661http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/18286529