{"doi":"10.3389/fonc.2023.1224491","title":"Somatic mutations of thymic epithelial tumors with myasthenia gravis","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>Thymic epithelial tumors are rare malignant neoplasms that are frequently associated with paraneoplastic syndromes, especially myasthenia gravis. GTF2I is an oncogene mutated in a subgroup of thymomas that is reputed to drive their growth. However, for GTF2I wild-type tumors, the relevant mutations remain to be identified.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed a meta-analysis and identified 4,208 mutations in 339 patients. We defined a panel of 63 genes frequently mutated in thymic epithelial tumors, which we used to design a custom assay for next-generation sequencing. We sequenced tumor DNA from 67 thymomas of patients with myasthenia gravis who underwent resection in our institution.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among the 67 thymomas, there were 238 mutations, 83 of which were in coding sequences. There were 14 GTF2I mutations in 6 A, 5 AB, 2 B2 thymomas, and one in a thymoma with unspecified histology. No other oncogenes showed recurrent mutations, while sixteen tumor suppressor genes were predicted to be inactivated. Even with a dedicated assay for the identification of specific somatic mutations in thymic epithelial tumors, only GTF2I mutations were found to be significantly recurrent.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our evaluation provides insights into the mutational landscape of thymic epithelial tumors, identifies recurrent mutations in different histotypes, and describes the design and implementation of a custom panel for targeted resequencing. These findings contribute to a better understanding of the genetic basis of thymic epithelial tumors and may have implications for future research and treatment strategies.</jats:p></jats:sec>","journal":"Frontiers in Oncology","year":2023,"id":625331,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1559554,"name":"Federico Cucchiara","orcid":null,"position":1,"is_corresponding":false},{"id":1617030,"name":"Sara Palumbo","orcid":null,"position":2,"is_corresponding":false},{"id":1617031,"name":"Giulia Tarrini","orcid":null,"position":3,"is_corresponding":false},{"id":1617032,"name":"Alessia Di Vita","orcid":null,"position":4,"is_corresponding":false},{"id":1526433,"name":"Fabio Coppedè","orcid":null,"position":5,"is_corresponding":false},{"id":1617033,"name":"Vanessa Nicolì","orcid":null,"position":6,"is_corresponding":false},{"id":846214,"name":"Melania Guida","orcid":"0000-0003-1968-5874","position":7,"is_corresponding":false},{"id":598672,"name":"Michelangelo Maestri","orcid":"0000-0003-0960-4938","position":8,"is_corresponding":false},{"id":401515,"name":"Roberta Ricciardi","orcid":"0009-0006-9506-0904","position":9,"is_corresponding":false},{"id":1617038,"name":"Vittorio Aprile","orcid":null,"position":10,"is_corresponding":false},{"id":1617040,"name":"Marcello C. Ambrogi","orcid":null,"position":11,"is_corresponding":false},{"id":1617043,"name":"Serena Barachini","orcid":null,"position":12,"is_corresponding":false},{"id":1108213,"name":"Marco Lucchi","orcid":"0000-0001-9909-6820","position":13,"is_corresponding":false},{"id":1559552,"name":"Iacopo Petrini","orcid":null,"position":14,"is_corresponding":false},{"id":1559553,"name":"Eleonora Pardini","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Somatic mutations of thymic epithelial tumors with myasthenia gravis","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>Thymic epithelial tumors are rare malignant neoplasms that are frequently associated with paraneoplastic syndromes, especially myasthenia gravis. GTF2I is an oncogene mutated in a subgroup of thymomas that is reputed to drive their growth. However, for GTF2I wild-type tumors, the relevant mutations remain to be identified.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed a meta-analysis and identified 4,208 mutations in 339 patients. We defined a panel of 63 genes frequently mutated in thymic epithelial tumors, which we used to design a custom assay for next-generation sequencing. We sequenced tumor DNA from 67 thymomas of patients with myasthenia gravis who underwent resection in our institution.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among the 67 thymomas, there were 238 mutations, 83 of which were in coding sequences. There were 14 GTF2I mutations in 6 A, 5 AB, 2 B2 thymomas, and one in a thymoma with unspecified histology. No other oncogenes showed recurrent mutations, while sixteen tumor suppressor genes were predicted to be inactivated. Even with a dedicated assay for the identification of specific somatic mutations in thymic epithelial tumors, only GTF2I mutations were found to be significantly recurrent.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our evaluation provides insights into the mutational landscape of thymic epithelial tumors, identifies recurrent mutations in different histotypes, and describes the design and implementation of a custom panel for targeted resequencing. 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