Abstract
There is limited understanding of the molecular pathogenesis of thymic epithelial tumors challenging the development of targeted therapies. These tumors exhibit chromosomal copy number alterations that increase in frequency and complexity with increasing aggressiveness of the histological subtype. They show low somatic mutation loads and recurrent mutations have been identified in a very limited number of genes, most commonly GTF2I. High-throughput studies have identified significant genomic and epigenomic differences among the different histological subtypes of thymomas, paving the way for a better understanding of tumorigenesis and progression. This chapter provides a concise overview of molecular genetic alterations of potential clinical significance.
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References
Radovich M, Pickering CR, Felau I, Ha G, Zhang H, et al. The integrated genomic landscape of thymic epithelial tumors. Cancer Cell. 2018;33:244–58.
Strobel P, Marx A, Badve S, Chan JKC, Chen G, Detterbeck F, et al. Thymomas Type A thymoma, including atypical variant. In: Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG, editors. WHO classification of tumours of lung, pleura, thymus and heart. 4th ed. Lyon: IARC; 2015. p. 187–92.
Petrini I, Meltzer PS, Kim IK, Lucchi M, Park KS, Fontanini G, et al. A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. Nat Genet. 2014;46:844–9.
Feng Y, Lei Y, Wu X, Huang Y, Rao H, Zhang Y, Wang F. GTF2I mutation frequently occurs in more indolent thymic epithelial tumors and predicts better prognosis. Lung Cancer. 2017;110:48–52.
Sakane T, Murase T, Okuda K, Saida K, Masaki A, Yamada T, et al. A mutation analysis of the EGFR pathway genes, RAS, EGFR, PIK3CA, AKT1, and BRAF, and TP53 gene in thymic carcinoma and thymoma type A/B3. Histopathology. 2019 Jun 10;75(5):755–66. https://doi.org/10.1111/his.13936.
Enkner F, Pichlhöfer B, Zaharie AT, Krunic M, Holper TM, Janik S, et al. Molecular profiling of thymoma and thymic carcinoma: genetic differences and potential novel therapeutic targets. Pathol Oncol Res. 2017;23:551–64.
Girard N, Shen R, Guo T, Zakowski MF, Heguy A, Riely GJ, et al. Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas. Clin Cancer Res. 2009;15:6790–9.
Rajan A, Girard N, Marx A. State of the art of genetic alterations in thymic epithelial tumors. J Thorac Oncol. 2014;9:S131–6.
Petrini I, Wang Y, Zucali PA, Lee HS, Pham T, Voeller D, Meltzer PS, Giaccone G. Copy number aberrations of genes regulating normal thymus development in thymic epithelial tumors. Clin Cancer Res. 2013;19:1960–71.
Aesif SW, Aubry MC, Yi ES, Kloft-Nelson SM, Jenkins SM, Spears GM, Greipp PT, Sukov WR, Roden AC. Loss of p16(INK4A) expression and homozygous CDKN2A deletion are associated with worse outcome and younger age in thymic carcinomas. J Thorac Oncol. 2017;12:860–71.
Ganci F, Vico C, Korita E, Sacconi A, Gallo E, Mori F, et al. MicroRNA expression profiling of thymic epithelial tumors. Lung Cancer. 2014;85:197–204.
Radovich M, Solzak JP, Hancock BA, Conces ML, Atale R, Porter RF, et al. A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas. Br J Cancer. 2016;114:477–84.
Bellissimo T, Ganci F, Gallo E, Sacconi A, Tito C, De Angelis L, et al. Thymic epithelial tumors phenotype relies on miR-145-5p epigenetic regulation. Mol Cancer. 2017;16:88. https://doi.org/10.1186/s12943-017-0655-2.
Wei J, Liu Z, Wu K, Yang D, He Y, Chen GG, Zhang J, Lin J. Identification of prognostic and subtype-specific potential miRNAs in thymoma. Epigenomics. 2017;9:647–57.
Bi Y, Meng Y, Niu Y, Li S, Liu H, He J, et al. Genome-wide DNA methylation profile of thymomas and potential epigenetic regulation of thymoma subtypes. Oncol Rep. 2019;41:2762–74.
Li S, Yuan Y, Xiao H, Dai J, Ye Y, Zhang Q, et al. Discovery and validation of DNA methylation markers for overall survival prognosis in patients with thymic epithelial tumors. Clin Epigenet. 2019;11:38. https://doi.org/10.1186/s13148-019-0619-z.
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Nambirajan, A., Singh, V., Jain, D. (2020). Molecular Pathology of Thymic Epithelial Tumors. In: Jain, D., Bishop, J.A., Wick, M.R. (eds) Atlas of Thymic Pathology. Springer, Singapore. https://doi.org/10.1007/978-981-15-3164-4_12
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DOI: https://doi.org/10.1007/978-981-15-3164-4_12
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