Abstract 1705: Genetic analysis of thymoma and thymic carcinoma

Abstract

[Background] Thymic epidermal tumors (thymoma and thymic cancer) are rare, and its genetic profiles are unclear. Molecular targeted therapy of thymic tumors has not been established. Clarifying a molecular alteration and to identify the novel targets for molecular targeted therapy is important. So, we conducted the next generation sequencing (NGS) analysis with surgically resected thymic tumor tissues. [Methods] From July 2013 to October 2018, thirty patients who were resected thymic epidermal tumors in our hospital were enrolled in this study. We got written informed consent from patients, and NGS analysis of extracted DNA sample was performed in 24 patients to the present time. DNA were extracted from fresh frozen surgically resected tissues (tumors and paired normal tissues) and DNA amplicon sequencing was performed with a custom panel of 53 cancer-related genes based on Ion AmpliSeq™ Cancer Hotspot Panel v2 comprising major oncogenes and tumor suppressor genes (including GTF2I). Sequencing was carried out with an Ion Torrent PGM™. Sequencing data were analyzed using Ion Reporter™. In addition, we collected the patient’s information (age, sex, Masaoka-Koga staging, World Health Organization (WHO) histologic classification, tumor size, and complication such as myasthenia gravis and pure red cell aplasia) from medical records. The study was approved by the Institutional Review Board (IRB) of the Nagasaki University Hospital. [Results] A total of 30 patients were enrolled in this study. The median age was 62 years old (range, 34-84 years old), patients characteristics were 9 male and 21 female, WHO histologic classification (type A, AB, B1, B2, B3, thymic carcinoma) was 1, 11, 4, 10, 2, 2, and Masaoka-Koga staging I, II, III, IV were 12, 6, 9, 3, respectively. Median tumor size was 47mm (range 11-110 mm). Moreover, complications were 7 myasthenia gravis, 4 acetylcholine receptor antibody-positive (do not confirm diagnossis of myasthenia gravis), 1 pure red cell aplasia, and 1 agranulocytosis. In NGS sequencing, the nonsynonymous mutations of HRAS and NRAS (HRAS Q61R, HRAS G13R, and NRAS Q61K) was detected in three patients. These RAS gene mutations were reported to be pathogenic in various malignancies. Low frequently DNMT3A mutation was detected in the other two patients, however this mutation were not validated in other methods. No genetic alterations were detected in the rest 19 patients. [Conclusion] The frequency of genetic alterations in thymic epidermal tumors was very low in this study, however, active mutations of RAS oncogene were detected in three patients. Although the RAS are still not established as treatment targets, it should be one of the interacting molecules. Further investigation is required to establish new therapeutic strategy according to the genetic alteration in thymic tumors. Citation Format: Hiroyuki Yamaguchi, Hiroshi Gyotoku, Hirokazu Taniguchi, Daisuke Sasaki, Midori Shimada, Yosuke Dotsu, Hiroaki Senju, Norihito Kaku, Takaya Ikeda, Minoru Fukuda, Katsunori Yanagihara, Hiroshi Mukae. Genetic analysis of thymoma and thymic carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1705.