title: Methylation profile of DNA repetitive elements in human testicular germ cell tumor.
abstract: Testicular germ cell tumors (TGCTs) have a unique epigenetic profile distinct from that of other types of cancer. To further evaluate epigenetics of TGCTs, this study examines DNA methylation patterns of DNA repetitive elements in TGCTs. Bisulfite genomic sequencing and combined bisulfite restriction analysis (COBRA) were used to analyze the methylation patterns of DNA repetitive elements (LINE1 and Alu repeats) in embryonal carcinoma (EC) derived cell lines, primary TGCT tissues, noncancerous testicular tissues adjacent to TGCTs and cancer cells derived from somatic tissues (testicular malignant lymphoma tissues and renal cell carcinoma cell lines). Through both bisulfite genomic sequencing and COBRA, LINE1 was extensively hypomethylated in both seminomatous and nonseminomatous TGCT tissues as well as EC cell lines. We studied two Alu repeats locating in the 5' end of E-cadherin and XIST by bisulfite genomic sequencing. These two Alu elements were extensively hypomethylated in seminomatous TGCTs, but methylated in nonseminomatous TGCTs, including two EC derived cell lines. This increased unmethylated profile in seminomatous TGCTs was observed also by COBRA for Alu repeats. Although partial demethylation of DNA repetitive elements was observed in cancer cells of somatic tissue origin, the degree of demethylation was more pronounced in TGCTs than in cancer cells of somatic tissue origin. We observed abnormal demethylation of DNA repetitive elements in some of the tissues adjacent to TGCTs. The results indicate that the underlying mechanisms to undergo or maintain demethylation of DNA repetitive sequences differ between TGCTs and cancer cells of somatic tissue origin.
authors.affiliation: Department of Urology, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ushida
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kawakami
authors.forename: Kahori
authors.initials: K
authors.lastname: Minami
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Chano
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Okabe
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Okada
authors.forename: Keisei
authors.initials: K
authors.lastname: Okamoto
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D018236:Carcinoma, Embryonal / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008223:Lymphoma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics*; D013737:Testis / Q000378:metabolism; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D034741:RNA, Small Interfering; C412484:DNMT3L protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases