Rare Frequency of Gene Variation and Survival Analysis in Thymic Epithelial Tumors

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2016 Oct 30

PMID 27789964

Citations 7

Authors

Zhengbo Song

Xinmin Yu

Yiping Zhang

Affiliations

Soon will be listed here.

Abstract

Objective: Thymic epithelial tumor (TET) is a rare mediastinal neoplasm and little is known about its genetic variability and prognostic factors. This study investigated the genetic variability and prognostic factors of TET.

Patients And Methods: We sequenced 22 cancer-related hotspot genes in TET tissues and matched normal tissues using Ampliseq Ion Torrent next-generation technology. Overall survival was evaluated using Kaplan-Meier methods and compared with log-rank tests.

Results: A histological analysis of 52 patients with a median age of 52 years showed 15 patients (28.8%) with thymic carcinoma, five with type A thymoma (9.6%), eight with type AB (15.4%), six with type B1 (11.5%), nine with type B2 (17.3%), and nine with type B3 thymoma (17.3%). Three gene mutations were identified, including two with mutation and one with mutation. The three patients with mutant genes included two cases of thymoma (one with and the other with mutation) in addition to a case of thymic carcinoma ( mutation). The 5-year survival rates were 77.7% in all patients. The 5-year survival rates were 93.3%, 90.0%, 76.9%, and 22.9% corresponding to Masaoka stages I, II, III, and IV (<0.001). The 5-year survival rates were 100%, 100%, 83.3%, 88.9%, 65.6%, and 60.9% in the histological subtypes of A, AB, B1, B2, and B3 thymomas, and thymic carcinoma, respectively (=0.012).

Conclusion: Hotspot gene mutations are rare in TET. and mutations represent candidate driver genes and treatment targets in TET. Masaoka stage and histological subtypes predict the survival of TET.

Citing Articles

Depiction of the Genetic Alterations and Molecular Landscapes of Thymic Epithelial Tumors: A Systematic Review and Meta-Analysis.

Wang X, Jin H, Feng X, Liang Z, Jin R, Li X Cancers (Basel). 2024; 16(17).

PMID: 39272824 PMC: 11394263. DOI: 10.3390/cancers16172966.

Genomic insights into molecular profiling of thymic carcinoma: a narrative review.

Takata S Mediastinum. 2024; 8:39.

PMID: 39161584 PMC: 11330910. DOI: 10.21037/med-24-5.

Chinese expert consensus on the diagnosis and treatment of thymic epithelial tumors.

Xu C, Zhang Y, Wang W, Wang Q, Li Z, Song Z Thorac Cancer. 2023; 14(12):1102-1117.

PMID: 36924056 PMC: 10125784. DOI: 10.1111/1759-7714.14847.

Targeted Next-Generation Sequencing of Thymic Epithelial Tumours Revealed Pathogenic Variants in , , , and in 30% of Thymic Carcinomas.

Szpechcinski A, Szolkowska M, Winiarski S, Lechowicz U, Wisniewski P, Knetki-Wroblewska M Cancers (Basel). 2022; 14(14).

PMID: 35884448 PMC: 9324890. DOI: 10.3390/cancers14143388.

Apatinib in patients with recurrent or metastatic thymic epithelial tumor: a single-arm, multicenter, open-label, phase II trial.

Song Z, Lou G, Wang Y, Yang Z, Wang W, Ji Y BMC Med. 2022; 20(1):154.

PMID: 35534877 PMC: 9088066. DOI: 10.1186/s12916-022-02361-w.

References

Welsh J, Thurman S, Howard S . Thymoma and multiple malignancies: a case of five synchronous neoplasms and literature review. Clin Med Res. 2005; 1(3):227-32. PMC: 1069048. DOI: 10.3121/cmr.1.3.227. View

Suzuki E, Sasaki H, Kawano O, Endo K, Haneda H, Yukiue H . Expression and mutation statuses of epidermal growth factor receptor in thymic epithelial tumors. Jpn J Clin Oncol. 2006; 36(6):351-6. DOI: 10.1093/jjco/hyl028. View

Yen Y, Lai W, Wu M, Lin M, Chang J, Hsu I . Thymic neuroendocrine carcinoma and thymoma are both associated with increased risk of extrathymic malignancy: a 20-year review of a single institution. Ann Thorac Surg. 2010; 91(1):219-25. DOI: 10.1016/j.athoracsur.2010.09.025. View

Fu H, Gu Z, Fang W, Fu J, Shen Y, Han Y . Long-Term Survival After Surgical Treatment of Thymic Carcinoma: A Retrospective Analysis from the Chinese Alliance for Research of Thymoma Database. Ann Surg Oncol. 2015; 23(2):619-25. DOI: 10.1245/s10434-015-4825-4. View

Pan C, Chen P, Wang L, Lee J, Chiang H . Expression of apoptosis-related markers and HER-2/neu in thymic epithelial tumours. Histopathology. 2003; 43(2):165-72. DOI: 10.1046/j.1365-2559.2003.01663.x. View

Engels E, Pfeiffer R . Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer. 2003; 105(4):546-51. DOI: 10.1002/ijc.11099. View

Thorvaldsdottir H, Robinson J, Mesirov J . Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2012; 14(2):178-92. PMC: 3603213. DOI: 10.1093/bib/bbs017. View

Scheffler M, Bos M, Gardizi M, Konig K, Michels S, Fassunke J . PIK3CA mutations in non-small cell lung cancer (NSCLC): genetic heterogeneity, prognostic impact and incidence of prior malignancies. Oncotarget. 2014; 6(2):1315-26. PMC: 4359235. DOI: 10.18632/oncotarget.2834. View

Bisagni G, Rossi G, Cavazza A, Sartori G, Gardini G, Boni C . Long lasting response to the multikinase inhibitor bay 43-9006 (Sorafenib) in a heavily pretreated metastatic thymic carcinoma. J Thorac Oncol. 2009; 4(6):773-5. DOI: 10.1097/JTO.0b013e3181a52e25. View

10.

Yoh K, Nishiwaki Y, Ishii G, Goto K, Kubota K, Ohmatsu H . Mutational status of EGFR and KIT in thymoma and thymic carcinoma. Lung Cancer. 2008; 62(3):316-20. DOI: 10.1016/j.lungcan.2008.03.013. View

11.

Strobel P, Hartmann M, Jakob A, Mikesch K, Brink I, Dirnhofer S . Thymic carcinoma with overexpression of mutated KIT and the response to imatinib. N Engl J Med. 2004; 350(25):2625-6. DOI: 10.1056/NEJM200406173502523. View

12.

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

13.

Petrini I, Meltzer P, Kim I, Lucchi M, Park K, Fontanini G . A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. Nat Genet. 2014; 46(8):844-9. PMC: 5705185. DOI: 10.1038/ng.3016. View

14.

Hishida T, Nomura S, Yano M, Asamura H, Yamashita M, Ohde Y . Long-term outcome and prognostic factors of surgically treated thymic carcinoma: results of 306 cases from a Japanese Nationwide Database Study. Eur J Cardiothorac Surg. 2015; 49(3):835-41. DOI: 10.1093/ejcts/ezv239. View

15.

Zettl A, Strobel P, Wagner K, Katzenberger T, Ott G, Rosenwald A . Recurrent genetic aberrations in thymoma and thymic carcinoma. Am J Pathol. 2000; 157(1):257-66. PMC: 1850202. DOI: 10.1016/S0002-9440(10)64536-1. View

16.

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

17.

Strobel P, Bargou R, Wolff A, Spitzer D, Manegold C, Dimitrakopoulou-Strauss A . Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience. Br J Cancer. 2010; 103(2):196-200. PMC: 2906735. DOI: 10.1038/sj.bjc.6605740. View

18.

Robinson J, Thorvaldsdottir H, Winckler W, Guttman M, Lander E, Getz G . Integrative genomics viewer. Nat Biotechnol. 2011; 29(1):24-6. PMC: 3346182. DOI: 10.1038/nbt.1754. View

19.

Li W, Miao Z, Liu X, Zhang Q, Sun L, Li P . Thymic carcinoma patients with myasthenia gravis exhibit better prognoses. Int J Clin Oncol. 2015; 21(1):75-80. DOI: 10.1007/s10147-015-0862-z. View

20.

Zhu L, Zhang J, Marx A, Weiss C, Fang W . Clinicopathological analysis of 241 thymic epithelial tumors-experience in the Shanghai Chest Hospital from 1997-2004. J Thorac Dis. 2016; 8(4):718-26. PMC: 4824732. DOI: 10.21037/jtd.2016.03.24. View