Department of Surgical Oncology, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, PR China.
Hum Pathol. 2011 Dec;42(12):1862-72. doi: 10.1016/j.humpath.2011.02.003. Epub 2011 Jun 11.
We investigated the spreading pattern of runt-related transcription factor-3 (RUNX3) C-phosphate-G (CpG) island (3478 base pairs) methylation in salivary gland adenoid cystic carcinoma. The methylation status of multiple regions within the runt-related transcription factor-3 promoter CpG island (3478 base pairs) was detected by real-time methylation-specific polymerase chain reaction, and the runt-related transcription factor-3 protein was detected with a Western blot in 19 salivary gland adenoid cystic carcinoma samples and the corresponding nonneoplastic salivary glands. The risk ratio between runt-related transcription factor-3 CpG island methylation and salivary gland adenoid cystic carcinoma progression was analyzed by the logistic analysis of variance model. A possible association between runt-related transcription factor-3 methylation, clinicopathologic parameters, and runt-related transcription factor-3 protein was analyzed. Hypermethylation initially occurs the most at the 5' region of runt-related transcription factor-3 CpG island before spreading to the transcription start site. The extent of methylation was found to be the highest in region nos. 1 and 2 among the successive 10 regions, which extend from the 5' region to the transcription start site within the runt-related transcription factor-3 CpG island. The extent of methylation is lowest at the transcription start site, both in salivary gland adenoid cystic carcinoma and in normal salivary glands. No methylation in the transcription start site was found in normal salivary glands. Logistic analysis of variance model indicates that the transcription start site within the runt-related transcription factor-3 promoter CpG island is critical for gene silencing. Western blots revealed that levels of the runt-related transcription factor-3 protein in adenoid cystic carcinoma samples are significantly lower than those in normal salivary glands (P < .001). Methylation of the runt-related transcription factor-3 CpG island spreads the most from 5' region to the transcription start site in adenoid cystic carcinoma tissues, and the transcription start site may be a critical region for the runt-related transcription factor-3 methylation. The spreading pattern of the runt-related transcription factor-3 methylation may play an a role in the progression of adenoid cystic carcinoma.
我们研究了 runt 相关转录因子 3（RUNX3）CpG 岛（3478 个碱基对）甲基化在唾液腺腺样囊性癌中的扩散模式。通过实时甲基化特异性聚合酶链反应检测 runt 相关转录因子 3 启动子 CpG 岛（3478 个碱基对）内多个区域的甲基化状态，并在 19 个唾液腺腺样囊性癌样本及其相应的非肿瘤唾液腺中用 Western blot 检测 runt 相关转录因子 3 蛋白。通过逻辑方差分析模型分析 runt 相关转录因子 3 CpG 岛甲基化与唾液腺腺样囊性癌进展之间的风险比。分析 runt 相关转录因子 3 甲基化与临床病理参数和 runt 相关转录因子 3 蛋白之间的可能关联。runt 相关转录因子 3 CpG 岛甲基化首先在 5'区域高度发生，然后扩散到转录起始位点。在连续 10 个区域中，从 5'区域到 runt 相关转录因子 3 CpG 岛内的转录起始位点，甲基化程度在区域 1 和 2 最高。在唾液腺腺样囊性癌和正常唾液腺中，转录起始位点的甲基化程度最低。在正常唾液腺中未发现转录起始位点的甲基化。逻辑方差分析模型表明，runt 相关转录因子 3 启动子 CpG 岛内的转录起始位点对于基因沉默至关重要。Western blot 显示，在腺样囊性癌样本中 runt 相关转录因子 3 蛋白的水平明显低于正常唾液腺（P <.001）。在腺样囊性癌组织中，runt 相关转录因子 3 CpG 岛的甲基化从 5'区域向转录起始位点扩散最多，而转录起始位点可能是 runt 相关转录因子 3 甲基化的关键区域。runt 相关转录因子 3 甲基化的扩散模式可能在腺样囊性癌的进展中发挥作用。
