Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy.
Department of Surgical, Medical, Molecular Pathology, University of Pisa, 56124 Pisa, Italy.
Biomolecules. 2021 Oct 19;11(10):1542. doi: 10.3390/biom11101542.
This study was designed to investigate whether (rearranged during transfection) mRNA over-expression could be considered an alternative driver event for the development of medullary thyroid carcinoma (MTC), and if different isoforms could play a role in MTC tumorigenesis. Eighty-three MTC patients, whose mutational profile was previously identified by next-generation sequencing (NGS) IONS5, were included in this study. Expression analysis was performed by the quantitative reverse transcription-polymerase chain reaction technique. expression levels were found to be significantly higher in cases with somatic mutations than in cases that were negative for somatic mutations ( = 0.003) as well as in cases with a somatic mutation, either in or than in cases negative for both these mutations ( = 0.01). All cases were positive for the isoform expression while only 72/83 (86.7%) were positive for isoform expression. A statistically significant higher expression of the isoform was found in cases positive for somatic mutation than in cases either positive for mutation ( = 0.0006) or negative for both mutations ( = 0.001). According to our data, gene over-expression does not play a role in MTC tumorigenesis, neither as an entire gene or as an isoform. At variance, the gene, and in particular the isoform, is expressed higher in mutated cases. On the basis of these results we can hypothesize that the overexpression of , and in particular of , could potentiate the transforming activity of mutated , making these cases more aggressive.
本研究旨在探究重排（rearranged during transfection）mRNA 过表达是否可被视为髓样甲状腺癌（medullary thyroid carcinoma，MTC）发生的替代驱动事件，以及不同的异构体是否在 MTC 肿瘤发生中发挥作用。本研究纳入了 83 例经下一代测序（next-generation sequencing，NGS）IONS5 鉴定突变谱的 MTC 患者。采用定量逆转录聚合酶链反应技术进行表达分析。结果显示，与 体细胞突变阴性病例相比（=0.003），以及与同时存在 体细胞突变和 体细胞突变的病例相比（=0.01），存在 体细胞突变的病例中 表达水平显著更高。所有病例均为 异构体表达阳性，而 83 例中仅有 72 例（86.7%）为 异构体表达阳性。与 突变阳性病例相比，存在 体细胞突变的病例中 异构体的表达水平更高，统计学差异显著（=0.0006），而与 突变和 突变均阴性的病例相比，统计学差异亦显著（=0.001）。根据我们的数据，基因过表达在 MTC 肿瘤发生中不起作用，无论是作为整个基因还是作为异构体。相反，基因，特别是 异构体，在 突变病例中表达更高。基于这些结果，我们可以假设，过表达 ，特别是 ，可能增强突变的转化活性，使这些病例更具侵袭性。
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