Sponziello Marialuisa, Durante Cosimo, Boichard Amelie, Dima Mariavittoria, Puppin Cinzia, Verrienti Antonella, Tamburrano Giulia, Di Rocco Giorgio, Redler Adriano, Lacroix Ludovic, Bidart Jean-Michel, Schlumberger Martin, Damante Giuseppe, Russo Diego, Filetti Sebastiano
Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", 00161 Roma, Italy.
Institut Gustave Roussy, Université Paris Sud, 94805 Villejuif, France.
Mol Cell Endocrinol. 2014 Jul 5;392(1-2):8-13. doi: 10.1016/j.mce.2014.04.016. Epub 2014 May 9.
Epigenetic control of gene expression plays a major influence in the development and progression of many cancer types. Aim of the present study was to investigate the expression of epigenetic regulators in a large cohort of medullary thyroid carcinomas (MTC), correlating the data with the clinical outcome and mutational status of the patients. Taqman Low Density Arrays (TLDAs) were used to analyze expression levels of several genes involved in the epigenetic control of transcription in a series of 54 MTCs. The patients cohort included 13 familial MTCs and 41 sporadic forms; 33 hosted a RET mutation and 13 a RAS somatic mutation. The expression profiling revealed in the more aggressive diseases (i.e. occurrence of metastases; persistent disease; disease-related death) a significant increase of EZH2 and SMYD3 gene expression. The increased levels of EZH2 and SMYD3 did not correlate significantly with mutational status of RET or RAS genes. Thus, the histone methyltransferases EZH2 and SMYD3 mRNA expression may represent useful prognostic biomarkers tailoring the most appropriate follow-up and timing of therapeutic approaches.
基因表达的表观遗传调控在多种癌症类型的发生和发展中发挥着重要影响。本研究的目的是调查一大群甲状腺髓样癌（MTC）中表观遗传调节因子的表达情况，并将数据与患者的临床结局和突变状态相关联。使用Taqman低密度阵列（TLDA）分析了一系列54例MTC中参与转录表观遗传调控的几个基因的表达水平。患者队列包括13例家族性MTC和41例散发性病例；33例存在RET突变，13例存在RAS体细胞突变。表达谱分析显示，在侵袭性更强的疾病（即发生转移、疾病持续、与疾病相关的死亡）中，EZH2和SMYD3基因表达显著增加。EZH2和SMYD3水平的升高与RET或RAS基因的突变状态无显著相关性。因此，组蛋白甲基转移酶EZH2和SMYD3 mRNA表达可能代表有用的预后生物标志物，有助于确定最合适的随访和治疗方法时机。
