Somatic mutations of thymic epithelial tumors with myasthenia gravis

Frontiers in Oncology

Oncology

Sara Palumbo¹  Serena Barachini¹  Iacopo Petrini²  Federico Cucchiara²  Eleonora Pardini²  Alessia Di Vita²  Giulia Tarrini²  Fabio Coppedè³  Vanessa Nicolì³  Melania Guida⁴  Roberta Ricciardi⁴  Michelangelo Maestri⁴  Marcello C. Ambrogi⁵  Marco Lucchi⁵  Vittorio Aprile⁵ 

[1] Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy;Medical Genetics, Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy;Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;Thoracic Surgery, Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy;

关键词: GTF2I;    thymoma;    next-generation sequencing;    myasthenia gravis;    thymic epithelial tumors;   

DOI  :  10.3389/fonc.2023.1224491

 received in 2023-05-17, accepted in 2023-07-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThymic 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.MethodsWe 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.ResultsAmong 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.ConclusionOur 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.

【 授权许可】

Unknown   
Copyright © 2023 Pardini, Cucchiara, Palumbo, Tarrini, Di Vita, Coppedè, Nicolì, Guida, Maestri, Ricciardi, Aprile, Ambrogi, Barachini, Lucchi and Petrini