DNA-methylation analysis as a tool for thymoma classification
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 diagn...
Gespeichert in:
| Hauptverfasser: | , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
29 November 2022
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| In: |
Cancers
Year: 2022, Jahrgang: 14, Heft: 23, Pages: 1-12 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers14235876 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers14235876 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/14/23/5876 
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| Verfasserangaben: | Timo Gaiser, Daniela Hirsch, Isabel Porth, Felix Sahm, Philipp Ströbel, Andreas von Deimling and Alexander Marx |
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| 520 | |a 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. | ||
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