Cross-platform array screening identifies COL1A2, THBS1, TNFRSF10D and UCHL1 as genes frequently silenced by methylation in melanoma.

Cross-platform array screening identifies COL1A2, THBS1, TNFRSF10D and UCHL1 as genes frequently silenced by methylation in melanoma.
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DOI:
10.1371/journal.pone.0026121
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Hayward NK
Hayward NK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bonazzi VF;Nancarrow DJ;Stark MS;Moser RJ;Boyle GM;Aoude LG;Schmidt C;Hayward NK

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肿瘤抑制基因(TSGs)的表观遗传调控已被证明在黑色素瘤形成中发挥核心作用。通过整合基因表达和甲基化阵列分析,我们确定了黑色素瘤中经常甲基化的新的候选基因。我们在大量黑色素瘤细胞系和切除的黑色素瘤中使用高度敏感的Sequenom Epityper检测验证了最有希望的基因的甲基化状态,并将结果与培养的黑色素细胞的结果进行了比较。我们发现UCHL1、COL1A2、THBS1和TNFRSF10D的转录本水平与启动子甲基化呈负相关。对于THBS1和UCHL1,这种甲基化对表达的影响在蛋白水平上得到了证实。这些候选tsg的鉴定和未来的研究旨在了解它们的沉默与黑色素瘤的发展之间的关系,这将增加我们对这种癌症病因的理解,并可能为其早期诊断提供工具。
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.
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