Distinct genomic features and mutational signatures of nucleotide excision repair and mismatch repair in thymoma

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.