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

Humans Thymoma / genetics Thymus Neoplasms / genetics Neoplasms, Glandular and Epithelial / genetics Genomics
genomic alterations microsatellite instability thymic epithelial tumors tumor mutational burden

Journal

ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685

Informations de publication

Date de publication:
10 2023
Historique:
received: 13 12 2022
revised: 25 05 2023
accepted: 02 08 2023
medline: 30 10 2023
pubmed: 13 9 2023
entrez: 13 9 2023
Statut: ppublish

Résumé

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.

Sections du résumé

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.

Identifiants

DOI: 10.1016/j.esmoop.2023.101627 PMID: 37703595 PMC: PMC10594028
pubmed: 37703595
pii: S2059-7029(23)00862-1
doi: 10.1016/j.esmoop.2023.101627
pmc: PMC10594028
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101627

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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Auteurs

K Kurokawa (K)

Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.

T Shukuya (T)

Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan. Electronic address: tshukuya@juntendo.ac.jp.

R A Greenstein (RA)

Foundation Medicine, Inc., Cambridge, USA.

B G Kaplan (BG)

Foundation Medicine, Inc., Cambridge, USA.

H Wakelee (H)

Department of Medicine, Division of Oncology, Stanford University, Stanford, USA.

J S Ross (JS)

Foundation Medicine, Inc., Cambridge, USA; Departments of Pathology and Urology, Upstate Medical University, Syracuse, USA.

K Miura (K)

Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.

K Furuta (K)

Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.

S Kato (S)

Department of Medical Oncology, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.

J Suh (J)

Genentech, South San Francisco, USA.

S Sivakumar (S)

Foundation Medicine, Inc., Cambridge, USA.

E S Sokol (ES)

Foundation Medicine, Inc., Cambridge, USA.

D P Carbone (DP)

Comprehensive Cancer Center, Division of Medical Oncology, The Ohio State University, Columbus, USA.

K Takahashi (K)

Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.

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questionsmedicales.fr › Hémopathies et maladies lymphatiques › Maladies lymphatiques › Tumeurs du thymus › Thymome › Genomic characterization of thymic epithelial...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Maladies lymphatiques › Tumeurs du thymus › Genomic characterization of thymic epithelial...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Genomic characterization of thymic epithelial...
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