Peric Jelena, Samaradzic Natalija, Skodric Trifunovic Vesna, Tosic Natasa, Stojsic Jelena, Pavlovic Sonja, Jovanovic Dragana
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
University Hospital of Pulmonology, Clinical Centre of Serbia, Belgrade, Serbia.
Arch Med Sci. 2020 Jul 3;20(3):909-917. doi: 10.5114/aoms.2020.96537. eCollection 2024.
Thymomas and thymic carcinoma (TC) are the most common neoplasms localised in the thymus. These diseases are poorly understood, but progress made in next-generation sequencing (NGS) technology has provided novel data on their molecular pathology.
Genomic DNA was isolated from formalin-fixed paraffin-embedded tumour tissue. We investigated somatic variants in 35 thymoma patients using amplicon-based TruSeq Amplicon Cancer Panel (TSACP) that covers 48 cancer related genes. We also analysed three samples from healthy individuals by TSACP platform and 32 healthy controls using exome sequencing.
The total number of detected variants was 4447, out of which 2906 were in the coding region (median per patient 83, range: 2-300) and 1541 were in the non-coding area (median per patient 44, range: 0-172). We identified four genes, , , , and , having more than 100 protein-changing variants. Additionally, more than 70% of the analysed cases harboured protein-changing variants in , and . Moreover, this study revealed 168 recurrent variants, out of which 15 were shown to be pathogenic. Comparison to controls revealed that the variants we reported in this study were somatic thymoma-specific variants. Additionally, we found that the presence of variants in 4 gene predicted shorter overall survival in thymoma patients.
The most frequently mutated genes in thymoma samples analysed in this study belong to the EGFR, ATM, and TP53 signalling pathways, regulating cell cycle check points, gene expression, and apoptosis. The results of our study complement the knowledge of thymoma molecular pathogenesis.
胸腺瘤和胸腺癌（TC）是胸腺最常见的肿瘤。这些疾病目前了解较少，但下一代测序（NGS）技术的进展为其分子病理学提供了新数据。
从福尔马林固定石蜡包埋的肿瘤组织中分离基因组DNA。我们使用覆盖48个癌症相关基因的基于扩增子的TruSeq扩增子癌症面板（TSACP），研究了35例胸腺瘤患者的体细胞变异。我们还通过TSACP平台分析了3例健康个体的样本，并使用外显子组测序分析了32例健康对照。
检测到的变异总数为4447个，其中2906个在编码区（每位患者中位数为83个，范围：2 - 300个），1541个在非编码区（每位患者中位数为44个，范围：0 - 172个）。我们鉴定出4个基因，即 、 、 和 ，具有超过100个蛋白质改变变异。此外，超过70%的分析病例在 、 和 中存在蛋白质改变变异。此外，本研究揭示了168个复发性变异，其中15个被证明是致病性的。与对照相比表明，我们在本研究中报告的变异是胸腺瘤特异性体细胞变异。此外，我们发现4个基因中变异的存在预测胸腺瘤患者的总生存期较短。
本研究分析的胸腺瘤样本中最常发生突变的基因属于表皮生长因子受体（EGFR）、共济失调毛细血管扩张症突变基因（ATM）和肿瘤蛋白p53（TP53）信号通路，这些通路调节细胞周期检查点、基因表达和细胞凋亡。我们的研究结果补充了胸腺瘤分子发病机制的知识。
