P1.14-28 Frequent Genetic Alterations and Their Clinical Significance in Patients with Thymic Epithelial Tumors

Abstract

Thymic epithelial tumors (TETs) are relatively rare neoplasms originating from the epithelial cells of the thymus. Due to the variety of different histology and low incidence, the current knowledge about the genetic alterations and prognostic factors of these tumors is still limited. Twenty-four specimens from Chinese patients with resected TETs were collected and sequenced by next-generation technology with 56 cancer-related hotspot genes. The somatic mutation data of TETs was also retrieved from TCGA database (The Cancer Genome Atlas) (n=123). Overall survival was evaluated using Kaplan-Meier methods and compared with log-rank tests. We analyzed 12 thymoma (type A, n =3; type AB, n=2; type B1/B2, n = 4; type B3, n = 3) and 12 thymic carcinoma in this study. At least one gene mutation was detected in 15 cases out of total 24 tumors. Half of thymoma and seventy-five percent of thymic carcinoma exhibited genetic alterations, respectively. Twenty-seven gene mutations were detected in total 24 tumors. The most frequent gene mutation of thymoma is BRCA1(25.0%, 3/12), while TP53 mutation is the most commen in thmic carcinoma (25.0%, 3/12). CDKN2A mutaion was exclusively observed in thymic carcinoma (16.7%, 2/12). Our and TCGA cohorts both demonstrated that TETs who presented TP53 mutation had a worse disease free survival and overall survival. Comprehensive genomic analysis suggests that the molecular phenotype of thymoma and thymic carcinoma has a distinct difference. TP53 and CDKN2A mutations might play an essential role in the pathogenesis in thymic carcinoma. Lastly, TP53 is the potential biomarker of poor prognosis in TETs.