Integrative Multiomic Classification Reveals Distinct Origins and Evolutionary Trajectories of Thymic Epithelial Tumors
Year: 2026
Type: article
Study design: Observational Study
Abstract: Thymic epithelial tumors (TET), comprising various histologic types of thymomas and thymic carcinomas, originate from thymic epithelial cells (TEC). Each histologic type is typically associated with a distinct immune cell composition and clinical manifestation. A better understanding of the cellular origins and molecular pathways underlying this heterogeneity is needed to improve patient stratification and treatment. In this study, we conducted an integrated genomic and transcriptomic analysis of 124 thymomas and 13 thymic carcinomas, including 20 newly sequenced cases, combined with 117 cases from publicly available datasets. Single-cell transcriptomic data from murine thymic tissues across developmental stages were incorporated to further investigate potential cells of origin. This approach stratified TETs into three subgroups with different possible origins: GTF2I-mutant (GTF2I-type) thymomas, copy number-altered (CN-type) thymomas, and thymic carcinomas. GTF2I-type thymomas, carrying hotspot GTF2I mutations, displayed transcriptional profiles resembling thymic epithelial progenitors. In contrast, CN-type thymomas, characterized by frequent copy-number alterations and IRS4 oncogene transcriptional activation, showed expression patterns similar to differentiated TECs. Thymic carcinomas, with high mutational burdens, exhibited profiles comparable with thymic tuft cells. The three subgroups also differed markedly in transcriptional programs, including lipid metabolism and immune phenotypes. Early acquisition of chromosomal copy-number alterations in CN-type thymomas further supported different evolutionary paths among subgroups. Together, these findings provide insights into the cellular origins and tumorigenic processes of TETs and underscore the value of integrative genomics for accurate cancer classification. SIGNIFICANCE: Thymic epithelial tumors can be classified into three subgroups based on genomic features and potential cells of origin, highlighting the importance of integrative analyses for accurate classification and therapeutic discovery.
Source: Cancer Research
Authors: Seongyeol Park, Kijong Yi, Jieun Lee, Myung Jin Yang, Joo-Hye Song, Joonoh Lim, Taewoo Kim, Seokhwi Kim, Su Yeon Kim, Hyung-Don Kim, Yoon Ho Kim, Sae Bom Lee, Yoo Jin Jung, Hansol Park, Jake June-Koo Lee, Yohan An, Jeonghwan Youk, Kwon Joong Na, Samina Park, Hyun Joo Lee, In Kyu Park, Chang Hyun Kang, Eui-Cheol Shin, Tae Min Kim, Won Do Heo, Charles Lee, Gou Young Koh, Sung-Yup Cho, Young Seok Ju, Young Tae Kim
Institutions: Korea Advanced Institute of Science and Technology, Seoul National University Hospital, Stanford Medicine, Stanford Cancer Institute, Stanford University, Harvard University, Seoul National University Bundang Hospital, Institute for Basic Science, Seoul National University, The Jackson Laboratory for Genomic Medicine
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: National Research Foundation, Seoul National University, Ministry of Science, ICT and Future Planning, Korea Institute of Science and Technology, Korea Institute of Science and Technology Information, Korea Health Industry Development Institute, National Research Foundation of Korea, Seoul National University Hospital, Institute for Basic Science, Korea Research Environment Open Network, College of Medicine, Seoul National University
OpenAlex ID: W7128645777