DNA-methylation analysis as a tool for thymoma classification

• Verfasst von: Gaiser, Timo [VerfasserIn]
• Verfasst von: Hirsch, Daniela [VerfasserIn]
• Verfasst von: Porth, Isabel [VerfasserIn]
• Verfasst von: Sahm, Felix [VerfasserIn]
• Verfasst von: Ströbel, Philipp [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Verfasst von: Marx, Alexander [VerfasserIn]
• Titel: DNA-methylation analysis as a tool for thymoma classification
• Verf.angabe: Timo Gaiser, Daniela Hirsch, Isabel Porth, Felix Sahm, Philipp Ströbel, Andreas von Deimling and Alexander Marx
• E-Jahr: 2022
• Jahr: 29 November 2022
• Umfang: 12 S.
• Fussnoten: Gesehen am 30.01.2023
• Titel Quelle: Enthalten in: Cancers
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2022
• Band/Heft Quelle: 14(2022), 23 vom: Nov., Artikel-ID 5876, Seite 1-12
• ISSN Quelle: 2072-6694
• DOI: doi:10.3390/cancers14235876
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: copy number
• Sach-SW: epigenetics
• Sach-SW: methylation
• Sach-SW: thymic epithelial tumors
• Sach-SW: thymoma
• K10plus-PPN: 1832667278

Abstract

Background: Thymomas are malignant thymic epithelial tumors that are difficult to diagnose due to their rarity and complex diagnostic criteria. They represent a morphologically heterogeneous class of tumors mainly defined by “organo-typical” architectural features and cellular composition. The diagnosis of thymoma is burdened with a high level of inter-observer variability and the problem that some type-specific morphological alterations are more on the continuum than clear-cut. Methylation pattern-based classification may help to increase diagnostic precision, particularly in borderline cases. Methods and Results: We applied array-based DNA methylation analysis to a set of 113 thymomas with stringent histological annotation. Unsupervised clustering and t-SNE analysis of DNA methylation data clearly segregated thymoma samples mainly according to the current WHO classification into A, AB, B1, B2, B2/B3, B3, and micronodular thymoma with lymphoid stroma. However, methylation analyses separated the histological subgroups AB and B2 into two methylation classes: mono-/bi-phasic AB-thymomas and conventional/“B1-like” B2-thymomas. Copy number variation analysis demonstrated methylation class-specific patterns of chromosomal alterations. Interpretation: Our study demonstrates that the current WHO classification is generally well reflected at the methylation level but suggests that B2- and AB-thymomas are (epi)genetically heterogeneous. Methylation-based classifications could help to refine diagnostic criteria for thymoma classification, improve reproducibility, and may affect treatment decisions.