Identification of differentially methylated CpG islands in prostate cancer.
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.
Yamada
Yasushi
Y
Second Department of Pathology, Mie University School of Medicine, Tsu, Japan.
Toyota
Minoru
M
Hirokawa
Yoshifumi
Y
Suzuki
Hiroyoshi
H
Takagi
Akimitsu
A
Matsuzaki
Takeshi
T
Sugimura
Yoshiki
Y
Yatani
Ryuichi
R
Shiraishi
Taizo
T
Watanabe
Masatoshi
M
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
D014408:Biomarkers, Tumor