Open AccessPromoter methylation profiling of 30 genes in human malignant melanoma
Author(s) -
Furuta Junichi,
Umebayashi Yoshihiro,
Miyamoto Kazuaki,
Kikuchi Kanako,
Otsuka Fujio,
Sugimura Takashi,
Ushijima Toshikazu
Publication year - 2004
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2004.tb03184.x
Subject(s) - methylation , biology , cpg site , dna methylation , gene , demethylation , cancer research , tumor suppressor gene , pten , microbiology and biotechnology , melanoma , gene silencing , promoter , gene expression , carcinogenesis , genetics , apoptosis , pi3k/akt/mtor pathway
Aberrant methylation and demethylation of promoter CpG islands lead to silencing of tumor‐suppressor genes and abnormal expression of normally methylated genes, respectively. Here, we analyzed human melanomas for their methylation and demethylation profiles. Methylation status of core regions in promoter CpG islands was examined for 20 (candidate) tumor‐suppressor genes, 4 genes that are not considered as tumor‐suppressors, but are frequently silenced in human cancers, and 6 normally methylated melanoma antigen genes ( MAGEs ). Analysis of 13 melanoma cell lines and 2 cultured normal human epidermal melanocytes (HEMs) showed that 9 tumor‐suppressor genes and all 4 non‐tumor‐suppressor genes were methylated in at least 1 cell line, but never in HEMs, and that all 6 MAGE genes were demethylated in 3 to 13 cell lines. Interestingly, we detected no methylation of MGMT, PTEN, MTAP and p27, which were previously reported as silenced in melanomas. Furthermore, 3 genes that were frequently methylated in the cell lines and 6 MAGE genes were analyzed in 25 surgical melanoma samples. RARB, RASSF1A and 3‐OST‐2 were methylated in 5 (20%), 9 (36%) and 14 (56%) samples, respectively. MAGE‐A1, A2, A3, B2, C1 and C2 were demethylated in 9 (36%), 22 (88%), 20 (80%), 7 (28%), 21 (84%) and 16 (64%) samples, respectively. At least 1 gene was methylated in 18 (72%) samples and at least 1 was demethylated in 24 (96%) samples. No correlation between frequent methylation and frequent demethylation was observed. These profiles showed that both aberrant methylation and demethylation occur widely in human melanomas.