胸腺上皮肿瘤（TETs）是罕见的发生于纵隔的肿瘤，包括胸腺癌和胸腺瘤。由于其罕见性，我们对TETs的基因组特征知之甚少。在本研究中，我们调查了一个大型综合基因组分析数据库中TETs的基因组特征，以真实世界中的情况为基础。我们包含了来自两个不同队列的数据：美国Foundation Medicine公司（FMI）和日本癌症基因组与先进治疗中心（C-CAT）。我们对被检测样本的253个靶向基因进行了全部异常类别的检测，并对肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）进行了评估。我们在本研究中共收集了794名患者的数据，其中FMI数据722例，C-CAT数据72例。在FMI数据中，胸腺癌中CDKN2A（39.9%），TP53（30.2%）和CDKN2B（24.6%）的异常频率较高，而胸腺瘤中TP53（7.8%），DNMT3A（6.8%）和CDKN2A（5.8%）的异常频率较高。TMB高（≥10个突变/Mb）和MSI在胸腺癌中分别占7.0%和2.3%，在胸腺瘤中分别占1.6%和0.3%。在C-CAT数据中，胸腺癌中CDKN2A（38.5%），TP53（36.5%）和CDKN2B（30.8%）的异常频率较高，而胸腺瘤中TSC1、SETD2和LTK（每种20.0%）的异常频率较高。据我们所知，这是迄今最大的对TETs的基因组异常、TMB和MSI状态进行研究的队列。本研究鉴定了在TETs中尚未被发现的潜在治疗靶点，为治疗发展带来了新的机会。

Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the genomic profiles of TETs. Herein, we investigated the genomic characteristics of TETs evaluated in a large comprehensive genomic profiling database in a real-world setting.We included data from two different cohorts: Foundation Medicine Inc. (FMI) in the United States and the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. Samples profiled were examined for all classes of alterations in 253 genes targeted across all assays. Tumor mutational burden (TMB) and microsatellite instability (MSI) were also evaluated.A total of 794 patients were collected in our study, including 722 cases from FMI and 72 cases from C-CAT. In the FMI data, CDKN2A (39.9%), TP53 (30.2%) and CDKN2B (24.6%) were frequently altered in thymic carcinoma, versus TP53 (7.8%), DNMT3A (6.8%), and CDKN2A (5.8%) in thymoma. TMB-high (≥10 mutations/Mb) and MSI were present in 7.0% and 2.3% of thymic carcinomas, and 1.6% and 0.3% of thymomas, respectively. Within C-CAT data, CDKN2A (38.5%), TP53 (36.5%) and CDKN2B (30.8%) were also frequently altered in thymic carcinoma, while alterations of TSC1, SETD2 and LTK (20.0% each) were found in thymoma.To the best of our knowledge, this is the largest cohort in which genomic alterations, TMB and MSI status of TETs were investigated. Potential targets for treatment previously unbeknownst in TETs are identified in this study, entailing newfound opportunities to advance therapeutic development.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.