Genetic profile of thymic epithelial tumors in the Japanese population: an exploratory study examining potential therapeutic targets.

Background: Thymic epithelial tumors (TETs) are prone to developing in East Asian populations. However, little is known about the genomic profile of TETs in East Asian populations, and the genomic aberrations in TETs have not yet been fully clarified. Thus, molecular targeted therapies for patients with TETs have not been established. This prospective study was conducted to explore the genetic abnormalities of surgically resected TETs in a Japanese cohort and to identify clues for carcinogenesis and potential therapeutic targets in TETs.

Methods: Genetic profiles of TETs were investigated using fresh-frozen specimens resected from operable cases with TETs. DNA sequencing was performed using a next-generation sequencing (NGS) gene panel test with Ion Reporter™ and CLC Genomics Workbench 11.0. The mutation sites were further confirmed by Sanger sequencing, digital droplet polymerase chain reaction (ddPCR), and TA cloning for validation.

Results: Among 43 patients diagnosed with anterior mediastinal tumors between January 2013 and March 2019, NGS and validation analyses were performed in 31 patients [29 thymomas and two thymic cancers (TCs)] who met the study criteria. Of these, 12 cases of thymoma types A, AB, B1, and B2 harbored the () mutation (L424H). Conversely, the mutation was not detected in type B3 thymoma or TC, suggesting that the mutation existed in indolent types of TETs. () mutations were detected in three cases [ () in two cases of type AB thymoma and ()] in one case of type B1 thymoma), and () mutation was present in one case of TC. All mutations were observed in mutated cases.

Conclusions: The mutation (L424H) is the most frequently occurring mutation in the limited histology of thymoma, consistent with those in the non-Asian population. and mutations co-occurred in cases harboring the mutation. These findings suggest that the existence of the mutation might be related to indolent types of TETs, and mutations could be candidates as therapeutic targets in TETs.