Open AccessCross-Platform Array Screening Identifies COL1A2, THBS1, TNFRSF10D and UCHL1 as Genes Frequently Silenced by Methylation in Melanoma
Author(s) -
Vanessa Bonazzi,
Derek J. Nancarrow,
Mitchell Stark,
Ralf Moser,
Glen M. Boyle,
Lauren G. Aoude,
Chris Schmidt,
Nicholas K. Hayward
Publication year - 2011
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0026121
Subject(s) - epigenetics , methylation , gene silencing , biology , melanoma , dna methylation , gene , cancer research , candidate gene , promoter , genetics , gene expression
Epigenetic regulation of tumor suppressor genes (TSGs) has been shown to play a central role in melanomagenesis. By integrating gene expression and methylation array analysis we identified novel candidate genes frequently methylated in melanoma. We validated the methylation status of the most promising genes using highly sensitive Sequenom Epityper assays in a large panel of melanoma cell lines and resected melanomas, and compared the findings with those from cultured melanocytes. We found transcript levels of UCHL1 , COL1A2 , THBS1 and TNFRSF10D were inversely correlated with promoter methylation. For THBS1 and UCHL1 the effect of this methylation on expression was confirmed at the protein level. Identification of these candidate TSGs and future research designed to understand how their silencing is related to melanoma development will increase our understanding of the etiology of this cancer and may provide tools for its early diagnosis.