Nikolic Nadja, Carkic Jelena, Ilic Dimitrijevic Ivana, Eljabo Najib, Radunovic Milena, Anicic Boban, Tanic Nasta, Falk Markus, Milasin Jelena
Department of Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia.
Clinic for Maxillofacial Surgery, School of Dental Medicine, University of Belgrade, Belgrade, Serbia.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2018 Jan;125(1):52-58. doi: 10.1016/j.oooo.2017.09.013. Epub 2017 Sep 28.
To investigate the prevalence of p16, p14, tumor protein p53 (TP53), and human telomerase reverse transcriptase (hTERT) promoter hypermethylation in mucoepidermoid carcinomas (MECs) and search for a possible association between methylation status and clinicopathological parameters.
DNA extracted from 35 formalin-fixed and paraffin-embedded MEC samples and 10 normal salivary gland (NSG) tissue samples was analyzed for the presence of promoter hypermethylation using methylation-specific polymerase chain reaction testing.
The percentages of gene hypermethylation in MECs versus NSGs were the following: p14: 100% versus 20% (P<.001); p16: 60% versus 20% (P = .035); hTERT: 54.3% versus 20% (P = .078); and TP53: 31.4% versus 30% (P = .981). Multiple sites were found to be methylated in 86% of MECs compared with 10% in NSGs (P< .001). TP53 and hTERT were more often methylated in lower clinical stages (P = .033 and P = .005, respectively).
Hypermethylation of p14 appears to be an important event in the development of mucoepidermoid carcinoma. High frequency of gene hypermethylation and high incidence of methylation at multiple sites point to the importance of epigenetic phenomena in the pathogenesis of MECs, although with modest impact on clinical parameters.
研究p16、p14、肿瘤蛋白p53（TP53）和人端粒酶逆转录酶（hTERT）启动子高甲基化在黏液表皮样癌（MEC）中的发生率，并寻找甲基化状态与临床病理参数之间的可能关联。
采用甲基化特异性聚合酶链反应检测，分析从35例福尔马林固定石蜡包埋的MEC样本和10例正常涎腺（NSG）组织样本中提取的DNA，以检测启动子高甲基化情况。
MEC与NSG中基因高甲基化的百分比分别为：p14：100%对20%（P<0.001）；p16：60%对20%（P = 0.035）；hTERT：54.3%对20%（P = 0.078）；TP53：31.4%对30%（P = 0.981）。86%的MEC中发现多个位点甲基化，而NSG中为10%（P<0.001）。TP53和hTERT在临床分期较低时更常发生甲基化（分别为P = 0.033和P = 0.005）。
p14高甲基化似乎是黏液表皮样癌发生发展中的一个重要事件。基因高甲基化频率高和多位点甲基化发生率高表明表观遗传现象在MEC发病机制中具有重要性，尽管对临床参数影响不大。
