Utility of MS-MLPA in DNA methylation profiling in primary laryngeal squamous cell carcinoma
Utility of MS-MLPA in DNA methylation profiling in primary laryngeal squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2014.01.003
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发表时间：
2014-04-01
期刊：
影响因子：
4.8
通讯作者：
Alvarez-Marcos, Cesar
中科院分区：
文献类型：
--
作者：
Lopez, Fernando;Sampedro, Teresa;Alvarez-Marcos, Cesar
目的：甲基化特异性多重结缔组织依赖性探针扩增（MS-MLPA）检测是一种很少用于喉鳞癌（LSCC） DNA甲基化分析的方法。材料和方法：采用MS-MLPA对53例LSCC和30例健康粘膜样品的基因甲基化进行了研究。使用亚硫酸氢盐焦磷酸测序和甲基化特异性证实了异常启动子超甲基化。结果：53例患者中有36例（68%）出现启动子超甲基化。CDKN2B（28%）、APC（17%）、RARb（15%）、DAPK1（11%）和CHFR（11%）是最常见的高甲基化。CHFR异常甲基化主要发生在晚期。甲基化特异性聚合酶链反应和亚硫酸盐焦磷酸测序证实了CDKN2B、APC和DAPK1的异常甲基化。结论：利用MS-MLPA对LSCC启动子甲基化分析发现CDKN2B、DAPK1、RARb、APC和CHFR是常见的表观遗传事件。鉴于表观遗传基因沉默的可逆性，这些基因作为生物标志物的临床意义与癌症治疗的有吸引力的靶点高度相关。(C) 2014 Elsevier Ltd.版权所有。
Objectives: Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay is a method that has rarely been exploited in DNA methylation profiling of laryngeal squamous cell carcinoma (LSCC).Material and methods: Methylation of the gene was investigated by MS-MLPA in a well-characterized series of 53 LSCC and 30 samples of healthy mucosa. Aberrant promoter hypermethylation was confirmed using bisulfite pyrosequencing, and methylation-specific.Results: Promoter hypermethylation was observed in 36 of the 53 patients (68%). CDKN2B (28%), APC (17%), RARb (15%), DAPK1 (11%) and CHFR (11%) were most frequently hypermethylated. Aberrant methylation of CHFR was mainly a late-stage event. Methylation-specific polymerase chain reaction and bisulfite pyrosequencing confirmed aberrant methylation for CDKN2B, APC and DAPK1.Conclusion: Promoter methylation profiling of LSCC using MS-MLPA identified CDKN2B, DAPK1, RARb, APC, and CHFR as frequent epigenetic events. The clinical implications of these genes as biomarkers are highly relevant as attractive targets for cancer therapy, given the reversible nature of epigenetic gene silencing. (C) 2014 Elsevier Ltd. All rights reserved.