Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Shanghai Tongshu Biotechnology Co., Ltd., Shanghai, China.
Cancer Med. 2023 May;12(9):10575-10586. doi: 10.1002/cam4.5795. Epub 2023 Mar 14.
Due to the low incidence and histological heterogeneity, the molecular features and underlying carcinogenic mechanisms of thymic epithelial tumors (TETs) are yet to be fully elucidated, especially for different subtypes of TETs.
Tumor tissue samples of 43 TETs with distinct histological subtypes were collected. We analyzed the molecular characteristics in different subtypes based on whole exome sequencing data.
The mutational profiles of the different subtypes of TETs varied. Compared with thymomas, thymic carcinomas (TCs) had a higher mutation frequency of MYO16 (33% vs. 3%, p = 0.024) and a lower frequency of ZNF729 mutations (0% vs. 35%, p = 0.044). No significant difference was observed in the median tumor mutation burden across different subtypes. The value of copy number variation burden, weighted genome instability index, and the number of amplified segments were all higher in TCs than thymomas, and they also tended to be higher in B3 thymoma than in non-B3 thymomas, while they had no significant differences between B3 thymoma and TCs. Clustering analyses revealed that Wnt, MAPK, Hedgehog, AMPK, and cell junction assembly signaling pathways were exclusively enriched in non-B3 thymomas, lysine degradation pathway in B3 thymoma, and extracellular matrix-receptor (ECM-receptor) interaction, positive regulation of cell cycle process, and activation of innate immune response pathways in TCs.
This study revealed distinct molecular landscapes of different subtypes of TETs, suggesting diverse pathogenesis of non-B3 thymomas, B3 thymomas, and TCs. Our findings warrant further validation in future large-scale studies and may provide a theoretical basis for potential personalized therapeutic strategies.
由于发病率低且组织学异质性，胸腺瘤上皮肿瘤（TETs）的分子特征和潜在致癌机制尚未完全阐明，尤其是对于不同亚型的 TETs。
收集了 43 例具有不同组织学亚型的 TET 肿瘤组织样本。我们基于全外显子组测序数据分析了不同亚型的分子特征。
不同亚型的 TETs 的突变谱不同。与胸腺瘤相比，胸腺癌（TCs）中 MYO16 的突变频率更高（33%比 3%，p=0.024），而 ZNF729 突变频率更低（0%比 35%，p=0.044）。不同亚型的肿瘤突变负担中位数无显著差异。拷贝数变异负担、加权基因组不稳定性指数和扩增片段数在 TCs 中均高于胸腺瘤，在 B3 胸腺瘤中也高于非 B3 胸腺瘤，而 B3 胸腺瘤与 TCs 之间无显著差异。聚类分析显示，非 B3 胸腺瘤中 Wnt、MAPK、Hedgehog、AMPK 和细胞连接组装信号通路明显富集，B3 胸腺瘤中赖氨酸降解通路富集，TCs 中细胞周期过程的正调控、固有免疫反应通路激活和细胞外基质受体（ECM-receptor）相互作用信号通路明显富集。
本研究揭示了不同亚型 TETs 的独特分子特征，提示非 B3 胸腺瘤、B3 胸腺瘤和 TCs 的发病机制不同。我们的研究结果需要在未来的大规模研究中进一步验证，这可能为潜在的个体化治疗策略提供理论依据。
