Genomic characterization of thymic epithelial tumors in a real-world dataset

K Kurokawa; T Shukuya; R A Greenstein; B G Kaplan; H Wakelee; J S Ross; K Miura; K Furuta; S Kato; J Suh; S Sivakumar; E S Sokol; D P Carbone; K Takahashi

doi:10.1016/j.esmoop.2023.101627

Genomic characterization of thymic epithelial tumors in a real-world dataset

ESMO Open. 2023 Oct;8(5):101627. doi: 10.1016/j.esmoop.2023.101627. Epub 2023 Sep 12.

Authors

K Kurokawa¹, T Shukuya², R A Greenstein³, B G Kaplan³, H Wakelee⁴, J S Ross⁵, K Miura¹, K Furuta⁶, S Kato⁷, J Suh⁸, S Sivakumar³, E S Sokol³, D P Carbone⁹, K Takahashi¹

Affiliations

¹ Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.
² Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan. Electronic address: tshukuya@juntendo.ac.jp.
³ Foundation Medicine, Inc., Cambridge, USA.
⁴ Department of Medicine, Division of Oncology, Stanford University, Stanford, USA.
⁵ Foundation Medicine, Inc., Cambridge, USA; Departments of Pathology and Urology, Upstate Medical University, Syracuse, USA.
⁶ Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
⁷ Department of Medical Oncology, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.
⁸ Genentech, South San Francisco, USA.
⁹ Comprehensive Cancer Center, Division of Medical Oncology, The Ohio State University, Columbus, USA.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: genomic alterations; microsatellite instability; thymic epithelial tumors; tumor mutational burden.

MeSH terms

Genomics
Humans
Neoplasms, Glandular and Epithelial* / genetics
Thymoma* / genetics
Thymoma* / pathology
Thymus Neoplasms* / genetics
Thymus Neoplasms* / pathology

Supplementary concepts

Thymic epithelial tumor