title: Identification of differentially methylated CpG islands in prostate cancer.
abstract: Epigenetic change such as DNA methylation is one important mechanism for regulating gene expression as genetic change, such as mutation or loss of heterozygosity. Methylation of cancer-related genes has been shown to play an important role in carcinogenesis and tumor progression. Using methylated CpG island amplification (MCA)/representational difference analysis (RDA), we identified four CpG islands in neurotrophin tyrosine kinase receptor type 2 (NTRK2), Protocadherine Flamingo1 and MFPC (Methylated Fragments in Prostate Cancer) 7 and 8. Bisulfite sequencing revealed that 2 regions of NTRK2 as well as MFPC7 and MFPC8 were aberrantly methylated in prostate cancer cell lines, and COBRA showed that 48 (76.24%), 37 (58.7%) and 14 (22.2%) of 63 prostate cancer tissues were methylated, respectively, for these sites. On the other hand, none of 13 benign prostate samples were methylated, except for 1 (7.7%) with NTRK2. For NTRK2, mRNA expression was negative in prostate cancer cell lines (LNCaP and DU145) but was recovered on a methyltransferase inhibitor (5-Aza-CdR) treatment. The role of NTRK2 within NTRK remains unclear. Our results suggest that these 3 hypermethylated DNA fragments also may be markers of prostate cancer detection.
authors.affiliation: Second Department of Pathology, Mie University School of Medicine, Tsu, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyota
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hirokawa
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Takagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sugimura
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Yatani
authors.forename: Taizo
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor