Evaluation of MYB promoter methylation in salivary adenoid cystic carcinoma
Evaluation of MYB promoter methylation in salivary adenoid cystic carcinoma
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DOI：
10.1016/j.oraloncology.2011.01.008
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发表时间：
2011-04-01
期刊：
影响因子：
4.8
通讯作者：
Ha, Patrick K.
中科院分区：
文献类型：
--
作者：
Shao, Chunbo;Bai, Weiliang;Ha, Patrick K.
转录因子 MYB 最近被认为是唾液腺腺样囊性癌 (ACC) 中一个有前途的候选癌基因。然而，ACC 中 MYB 的上调不能仅用其 30 末端的删除来解释。人们普遍认为启动子甲基化状态可以调节基因的转录，尤其是在人类癌症中。因此，了解 MYB 启动子去甲基化是否可以解释 ACC 中 MYB 的过表达非常重要。通过使用 Methprimer 程序，我们在 MYB 启动子中鉴定出了 9 个 CpG 岛。所有这些 CpG 岛均位于相对于 MYB 转录起始位点的 -864 至 +2082 nt 区域内。然后，我们使用亚硫酸氢盐基因组测序来评估 18 个原发性 ACC 肿瘤、13 个正常唾液腺组织和 9 个癌细胞系中 MYB CpG 岛的甲基化水平。使用细胞系，我们还确定了相对 MYB 表达水平并将其与甲基化水平相关联。通过亚硫酸氢盐基因组测序，我们发现 ACC 或正常唾液腺组织中 MYB 的 CpG 岛未检测到甲基化。测试的细胞系中存在不同程度的 MYB 表达，但这些细胞系均未表现出启动子甲基化。启动子低甲基化似乎不能解释 ACC 中 MYB 的差异表达。需要提出一种替代机制来控制 ACC 中 MYB 的转录。 (C) 2011 Elsevier Ltd. 保留所有权利。
The transcription factor MYB was recently proposed to be a promising oncogene candidate in salivary gland adenoid cystic carcinoma (ACC). However, the up-regulation of MYB in ACC could not be explained solely by deletion of its 30 end. It is widely accepted that the promoter methylation status can regulate the transcription of genes, especially in human cancers. Therefore, it is important to know whether MYB promoter demethylation could explain the over-expression of MYB in ACC. By using the Methprimer program, we identified nine CpG islands in the promoter of MYB. All of these CpG islands were located within the -864 to +2082 nt region relative to the transcription start site of MYB. We then used bisulfite genomic sequencing to evaluate the methylation levels of the CpG islands of MYB in 18 primary ACC tumors, 13 normal salivary gland tissues and nine cancer cell lines. Using cell lines, we also determined the relative MYB expression levels and correlated these with the methylation levels. With bisulfite genomic sequencing, we found no detectable methylation in the CpG islands of MYB in either ACC or normal salivary gland tissues. There was a variable degree of MYB expression in the cell lines tested, but none of these cell lines demonstrated promoter methylation. Promoter hypomethylation does not appear to explain the differential expression of MYB in ACC. An alternative mechanism needs to be proposed for the transcriptional control of MYB in ACC. (C) 2011 Elsevier Ltd. All rights reserved.