Genomic Insights into Molecular Profiling of Thymic Carcinoma: a Narrative Review

Overview

Journal Mediastinum

Publisher AME Publishing Company

Date 2024 Aug 20

PMID 39161584

Authors

So Takata

Affiliations

Soon will be listed here.

Abstract

Background And Objective: Thymic carcinoma is an exceptionally rare cancer, with an annual incidence of just 0.15-0.29 per 100,000 people. Owing to its rarity, only few proven treatments have been developed. Understanding its genetic profile is crucial for the development of targeted therapies. However, limited studies have exclusively examined thymic carcinoma mutations, with most investigation combining thymomas and thymic carcinomas. This paper reviews findings from genetic studies focusing on thymic carcinoma alone and compares them to those of thymoma.

Methods: We conducted a PubMed search for relevant English studies on thymic carcinoma genomics. Then, key papers utilizing target sequencing or whole-exome sequencing were analyzed.

Key Content And Findings: The most frequently mutated genes were , , , , , , , , and . and are correlated with poor prognosis. , which regulates signaling related with proliferation and interacts with AIRE expression and T cell development, might predict the immunotherapy response. mutations might enable targeted therapy. , , , and regulate epigenetics, suggesting disruption of these mechanisms. Higher tumor mutational burden (TMB) and 16q loss distinguish thymic carcinoma from thymoma. Although some copy number aberrations are shared, thymic carcinoma exhibits a mutational profile distinct from that of thymoma.

Conclusions: Thymic carcinoma demonstrates a unique genomic landscape, suggesting a molecular pathogenesis distinct from that of thymoma. Our findings revealed prognostic biomarkers such as / and potential therapeutic targets such as . Because thymic carcinoma is extremely rare, sharing molecular profiling data could provide valuable insights into the molecular mechanisms driving the development of these tumors.

References

Alameda J, Moreno-Maldonado R, Navarro M, Bravo A, Ramirez A, Page A . An inactivating CYLD mutation promotes skin tumor progression by conferring enhanced proliferative, survival and angiogenic properties to epidermal cancer cells. Oncogene. 2010; 29(50):6522-32. DOI: 10.1038/onc.2010.378. View

Koizumi T, Otsuki K, Tanaka Y, Noguchi T, Fukushuima T, Kobayashi T . National incidence and initial therapy for thymic carcinoma in Japan: based on analysis of hospital-based cancer registry data, 2009-2015. Jpn J Clin Oncol. 2020; 50(4):434-439. DOI: 10.1093/jjco/hyz203. View

Conforti F, Pala L, De Pas T, He Y, Giaccone G . Investigational drugs for the treatment of thymic cancer: a focus on phase 1 and 2 clinical trials. Expert Opin Investig Drugs. 2022; 31(9):895-904. DOI: 10.1080/13543784.2022.2113373. View

Marin-Rubio J, Raote I, Inns J, Dobson-Stone C, Rajan N . CYLD in health and disease. Dis Model Mech. 2023; 16(6). PMC: 10320722. DOI: 10.1242/dmm.050093. View

Kelly R, Petrini I, Rajan A, Wang Y, Giaccone G . Thymic malignancies: from clinical management to targeted therapies. J Clin Oncol. 2011; 29(36):4820-7. PMC: 3675690. DOI: 10.1200/JCO.2011.36.0487. View

Song Z, Yu X, Zhang Y . Rare frequency of gene variation and survival analysis in thymic epithelial tumors. Onco Targets Ther. 2016; 9:6337-6342. PMC: 5072509. DOI: 10.2147/OTT.S108749. View

Radovich M, Pickering C, Felau I, Ha G, Zhang H, Jo H . The Integrated Genomic Landscape of Thymic Epithelial Tumors. Cancer Cell. 2018; 33(2):244-258.e10. PMC: 5994906. DOI: 10.1016/j.ccell.2018.01.003. View

Figueroa M, Abdel-Wahab O, Lu C, Ward P, Patel J, Shih A . Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010; 18(6):553-67. PMC: 4105845. DOI: 10.1016/j.ccr.2010.11.015. View

Wang H, Xu X, Luo L, Wang C, Jiang Z, Lin Y . Mutational landscape of thymic epithelial tumors in a Chinese population: insights into potential clinical implications. Gland Surg. 2021; 10(4):1410-1417. PMC: 8102230. DOI: 10.21037/gs-21-157. View

10.

Sakane T, Murase T, Okuda K, Saida K, Masaki A, Yamada T . 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; 75(5):755-766. DOI: 10.1111/his.13936. View

11.

Fang W, Wu C, Sun Q, Gu Z, Zhu L, Mao T . Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas. Front Immunol. 2021; 12:748820. PMC: 8635231. DOI: 10.3389/fimmu.2021.748820. View

12.

Umemura S, Zhu J, Chahine J, Kallakury B, Chen V, Kim I . Downregulation of CYLD promotes IFN-γ mediated PD-L1 expression in thymic epithelial tumors. Lung Cancer. 2020; 147:221-228. DOI: 10.1016/j.lungcan.2020.07.018. View

13.

Ardeshir-Larijani F, Schneider B, Althouse S, Radovich M, Masood A, Perna F . Clinicogenomic Landscape of Metastatic Thymic Epithelial Tumors. JCO Precis Oncol. 2023; 7:e2200465. PMC: 10309539. DOI: 10.1200/PO.22.00465. View

14.

Shitara M, Okuda K, Suzuki A, Tatematsu T, Hikosaka Y, Moriyama S . Genetic profiling of thymic carcinoma using targeted next-generation sequencing. Lung Cancer. 2014; 86(2):174-9. DOI: 10.1016/j.lungcan.2014.08.020. View

15.

Conforti F, Pala L, Giaccone G, De Pas T . Thymic epithelial tumors: From biology to treatment. Cancer Treat Rev. 2020; 86:102014. DOI: 10.1016/j.ctrv.2020.102014. View

16.

Maniar R, Loehrer Sr P . Understanding the landscape of immunotherapy in thymic epithelial tumors. Cancer. 2023; 129(8):1162-1172. DOI: 10.1002/cncr.34678. View

17.

Tateo V, Manuzzi L, Parisi C, De Giglio A, Campana D, Pantaleo M . An Overview on Molecular Characterization of Thymic Tumors: Old and New Targets for Clinical Advances. Pharmaceuticals (Basel). 2021; 14(4). PMC: 8066729. DOI: 10.3390/ph14040316. View

18.

Yemelyanova A, Vang R, Kshirsagar M, Lu D, Marks M, Shih I . Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis. Mod Pathol. 2011; 24(9):1248-53. DOI: 10.1038/modpathol.2011.85. View

19.

Girard N, Shen R, Guo T, Zakowski M, Heguy A, Riely G . Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas. Clin Cancer Res. 2009; 15(22):6790-9. PMC: 2783876. DOI: 10.1158/1078-0432.CCR-09-0644. View

20.

Girard N, Basse C, Schrock A, Ramkissoon S, Killian K, Ross J . Comprehensive Genomic Profiling of 274 Thymic Epithelial Tumors Unveils Oncogenic Pathways and Predictive Biomarkers. Oncologist. 2022; 27(11):919-929. PMC: 9632319. DOI: 10.1093/oncolo/oyac115. View