title: Hypermethylation of CDH13, DKK3 and FOXL2 promoters and the expression of EZH2 in ovary granulosa cell tumors.
abstract: Aberrant epigenetic modification is associated with the development and progression of cancer. Hypermethylation of tumor suppressor gene promoters and cooperative histone modification have been considered to be the primary mechanisms of epigenetic modification. Ovary granulosa cell tumors (GCTs) are relatively rare, accounting for ~3% of all ovarian malignancies. The present study assessed hypermethylation of the cadherin 13 (CDH13), dickkopf WNT signaling pathway inhibitor 3 (DKK3) and forkhead box L2 (FOXL2) promoters in 30 GCT tissues and 30 healthy control tissues using methylation-specific polymerase chain reaction analysis. The data showed that the frequencies of CDH13, DKK3 and FOXL2 promoter methylation were significantly higher in the GCT tissues, compared with the healthy control tissues (86.67, vs. 23.33%; 80, vs. 26.67% and 66.67, vs. 20%, respectively; P<0.001). Immunostaining of enhancer of zeste homolog 2 (EZH2), a histone H3K27 methyltransferase, showed that the EZH2 protein was expressed in 11 of the 30 GCT tissue samples, whereas no EZH2 protein was expressed in the 30 healthy control tissues (P<0.01). These data suggested that hypermethylation of the CDH13, DKK3 and FOXL2 gene promoters, and overexpression of the EZH2 protein were involved in the development of GCT.
authors.affiliation: Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obsterics, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research for Cancer, Tianjin 300060, P.R. China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shandong Shanxian Central Hospital, Heze, Shandong 274300, P.R. China.
authors.forename: Pengmu
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Pathology, Shandong Shanxian Central Hospital, Heze, Shandong 274300, P.R. China.
authors.forename: Xun
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Pathology, Shandong Shanxian Central Hospital, Heze, Shandong 274300, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Tingguo
authors.initials: T
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D015415:Biomarkers; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D018925:Chemokines; D019175:DNA Methylation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006106:Granulosa Cell Tumor / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012008:Recurrence; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D015820:Cadherins; D018925:Chemokines; C498624:DKK3 protein, human; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C099972:H-cadherin; D036341:Intercellular Signaling Peptides and Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein