title: Promoter hypermethylation of multiple genes in hydatidiform mole and choriocarcinoma.
abstract: The methylation status of genes in hydatidiform mole and choriocarcinoma and its significance is relatively unexplored. We investigated the methylation status of the promoter regions of six genes, p16, HIC-1, TIMP3, GSTP1, death-associated protein kinase (DAPK), and E-cadherin in 54 hydatidiform moles, five choriocarcinomas, and 10 first trimester placenta by methylation-specific polymerase chain reaction (PCR). Immunohistochemical expression of p16, TIMP3, and E-cadherin, and quantitative real-time RT-PCR of p16 was also performed. Among the six genes examined, the promoter region of four genes (E-cadherin, HIC-1, p16, TIMP3) in choriocarcinoma and three genes (E-cadherin, HIC-1, p16) in hydatidiform mole exhibited aberrant methylation whereas none was hypermethylated in normal placenta. There was a significant correlation between methylation and reduced expression of p16, E-cadherin, and TIMP3 (P < 0.001). Fifteen of the 54 patients with hydatidiform mole developed gestational trophoblastic neoplasia requiring chemotherapy. Promoter hypermethylation of p16 alone, or combined with E-cadherin, was significantly correlated to such development (P = 0.001, 0.0005, respectively). Hypermethylation of multiple genes, especially p16, might be related to the subsequent development of gestational trophoblastic neoplasia.
authors.affiliation: Department of Pathology, Hong Kong Jockey Club Clinical Research Centre, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Xue
authors.forename: Kelvin Y K
authors.initials: KY
authors.lastname: Chan
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Feng
authors.forename: Pui-Man
authors.initials: PM
authors.lastname: Chiu
authors.forename: Hextan Y S
authors.initials: HY
authors.lastname: Ngan
authors.forename: Sai-Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Annie N Y
authors.initials: AN
authors.lastname: Cheung
mesh_terms: D051017:Apoptosis Regulatory Proteins; D015820:Cadherins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002822:Choriocarcinoma / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D064550:Death-Associated Protein Kinases; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics; D051741:Kruppel-Like Transcription Factors; D010920:Placenta / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D004268:DNA-Binding Proteins; C499808:HIC1 protein, human; D007527:Isoenzymes; D051741:Kruppel-Like Transcription Factors; D019717:Tissue Inhibitor of Metalloproteinase-3; D014157:Transcription Factors; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases