Department of Pathology, Dunedin School of Medicine, University of Otago, 56 Hanover Street, Dunedin, 9054, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, Level 2, 3A Symonds Street, Auckland, New Zealand.
Clin Epigenetics. 2019 Aug 5;11(1):114. doi: 10.1186/s13148-019-0710-5.
Characteristic DNA methylation differences have been identified between primary and metastatic melanomas at EBF3 and/or TBC1D16 gene loci. To further evaluate whether these epigenetic changes may act more generally as drivers of tumour onset and metastasis, we have investigated DNA methylation changes involving EBF3 and TBC1D16 in additional publicly available data of multiple different tumour types.
Promoter hypermethylation and gene body hypomethylation of EBF3 were observed in a number of metastatic tumour types, when compared to normal or primary tumour tissues, as well as in tumour vs normal tissues and in a colorectal primary/metastasis pair, although not all tumour samples or primary/metastasis cancer pairs exhibited altered patterns of EBF3 methylation. In addition, hypomethylation of TBC1D16 was observed in multiple tumours, including a breast cancer primary/metastasis pair, and to a lesser degree in melanoma, although again not all tumours or cancer primary/metastasis pairs exhibited altered patterns of methylation.
These findings suggest characteristic DNA methylation changes in EBF3 and TBC1D16 are relatively common tumour-associated epigenetic events in multiple tumour types, which is consistent with a potential role as more general drivers of tumour progression.
在 EBF3 和/或 TBC1D16 基因座中,已经鉴定出原发性和转移性黑色素瘤之间具有特征性的 DNA 甲基化差异。为了进一步评估这些表观遗传变化是否更普遍地作为肿瘤发生和转移的驱动因素,我们研究了 EBF3 和 TBC1D16 中涉及的 DNA 甲基化变化,这些变化涉及多个不同肿瘤类型的其他公开可用数据。
与正常或原发性肿瘤组织相比,在许多转移性肿瘤类型中观察到 EBF3 的启动子过度甲基化和基因体低甲基化,以及肿瘤与正常组织之间,以及结直肠原发性/转移性对中,尽管并非所有肿瘤样本或原发性/转移性癌症对都表现出 EBF3 甲基化模式的改变。此外,在多种肿瘤中观察到 TBC1D16 的低甲基化,包括乳腺癌原发性/转移性对,在黑色素瘤中程度较低,但同样并非所有肿瘤或癌症原发性/转移性对都表现出改变的甲基化模式。
这些发现表明,EBF3 和 TBC1D16 中的特征性 DNA 甲基化变化在多种肿瘤类型中是相对常见的肿瘤相关表观遗传事件,这与作为肿瘤进展更普遍驱动因素的潜在作用一致。