title: Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas.
abstract: Aberrant methylation of promoter CpG islands (CGI) is involved in silencing of tumor suppressor genes and is also a potential cancer biomarker. Here, to identify CGIs aberrantly methylated in human melanomas, we did a genome-wide search using methylation-sensitive representational difference analysis. CGIs in putative promoter regions of 34 genes (ABHD9, BARHL1, CLIC5, CNNM1, COL2A1, CPT1C, DDIT4L, DERL3, DHRS3, DPYS, EFEMP2, FAM62C, FAM78A, FLJ33790, GBX2, GPR10, GPRASP1, HOXA9, HOXD11, HOXD12, HOXD13, p14ARF, PAX6, PRDX2, PTPRG, RASD1, RAX, REC8L1, SLC27A3, TGFB2, TLX2, TMEM22, TMEM30B, and UNC5C) were found to be methylated in at least 1 of 13 melanoma cell lines but not in two cultured normal melanocytes. Among these genes, Peroxiredoxin 2 (PRDX2) was expressed in normal melanocytes, and its expression was lost in melanomas with methylation. The loss of expression was restored by treatment of melanomas with a demethylating agent 5-aza-2'-deoxycytidine. In surgical melanoma specimens, methylation of PRDX2 was detected in 3 of 36 (8%). Furthermore, immunohistochemical analysis of PRDX2 showed that disappearance of immunoreactivity tends to associate with its methylation. PRDX2 was recently reported to be a negative regulator of platelet-derived growth factor signaling, and its silencing was suggested to be involved in melanomas. On the other hand, 12 CGIs were methylated in >or=9 of the 13 melanoma cell lines and are considered as candidate melanoma biomarkers.
authors.affiliation: Carcinogenesis Division, National Cancer Center Research Institute, Tsukiji, Tokyo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Furuta
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Nobeyama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Umebayashi
authors.forename: Fujio
authors.initials: F
authors.lastname: Otsuka
authors.forename: Kanako
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D020868:Gene Silencing; D015894:Genome, Human; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D010544:Peroxidases / Q000096:biosynthesis / Q000235:genetics*; D054464:Peroxiredoxins; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor; D006360:Heat-Shock Proteins; D010544:Peroxidases; C086065:PRDX2 protein, human; D054464:Peroxiredoxins