Cheng Po-Liang, Wang Wei-Jan, Chuang Cheng-Yen, Lin Chih-Hung, Huang Chih-Yang, Hsiao Tzu-Hung, Hsu Chung-Ping
Department of Medical Research, Taichung Veterans General Hospital Taichung, Taiwan.
Department of Biological Science and Technology, China Medical University Taichung, Taiwan.
Am J Cancer Res. 2025 Mar 15;15(3):1189-1200. doi: 10.62347/ZWSB8391. eCollection 2025.
Thymoma is a rare malignancy with an unclear etiology of occurrence and development. We observed a higher incidence of thymoma in the Taiwanese population compared to other Western populations, suggesting the existence of different genomic features. Since most genomic studies are based on Western populations, we aimed to characterize the genomic profile of the Taiwanese population and compare it to the TCGA cohort in this study. We analyzed the genome of 47 thymoma patients using the Tumor Mutational Burden Panel to discover the genetic profile of the Taiwanese population. We also characterized the mutational signatures of these samples. Additionally, we leveraged RNA seq to estimate the gene expression profile and explored the featured pathways of thymoma in the Taiwanese population through gene set enrichment analysis.We identified several frequently mutated genes related to transcription, such as FAT1, KMT2D, and ZFHX3, as well as consensus mutational signatures associated with nucleotide excision repair (NER) and mismatch repair (MMR) deficiency. Our study also revealed increased activity of NER and MMR functions in our study cohort. Upon comparison with the TCGA cohort, we found dramatic differences in the most frequently mutated genes and mutational profiles between the Taiwanese and TCGA cohorts. Furthermore, we identified mismatch repair deficiency as a Taiwanese population-specific mutational signature with higher activity. These results highlight the distinct genomic background and molecular mechanisms of thymoma in the Taiwanese population, which may contribute to the development of new diagnostic and therapeutic strategies in the future.
胸腺瘤是一种罕见的恶性肿瘤，其发生和发展的病因尚不清楚。我们观察到台湾人群中胸腺瘤的发病率高于其他西方人群，这表明存在不同的基因组特征。由于大多数基因组研究基于西方人群，我们旨在表征台湾人群的基因组概况，并在本研究中将其与TCGA队列进行比较。我们使用肿瘤突变负担面板分析了47例胸腺瘤患者的基因组，以发现台湾人群的基因特征。我们还表征了这些样本的突变特征。此外，我们利用RNA测序来估计基因表达谱，并通过基因集富集分析探索台湾人群中胸腺瘤的特征性途径。我们鉴定了几个与转录相关的频繁突变基因，如FAT1、KMT2D和ZFHX3，以及与核苷酸切除修复（NER）和错配修复（MMR）缺陷相关的共识突变特征。我们的研究还揭示了我们研究队列中NER和MMR功能的活性增加。与TCGA队列相比，我们发现台湾队列和TCGA队列在最频繁突变的基因和突变谱方面存在显著差异。此外，我们将错配修复缺陷鉴定为台湾人群特有的具有较高活性的突变特征。这些结果突出了台湾人群中胸腺瘤独特的基因组背景和分子机制，这可能有助于未来新诊断和治疗策略的发展。
