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| Item Type: | Article |
|---|---|
| Title: | DNA methylation-based classification of sinonasal tumors |
| Creators Name: | Jurmeister, P. and Glöß, S. and Roller, R. and Leitheiser, M. and Schmid, S. and Mochmann, L.H. and Payá Capilla, E. and Fritz, R. and Dittmayer, C. and Friedrich, C. and Thieme, A. and Keyl, P. and Jarosch, A. and Schallenberg, S. and Bläker, H. and Hoffmann, I. and Vollbrecht, C. and Lehmann, A. and Hummel, M. and Heim, D. and Haji, M. and Harter, P. and Englert, B. and Frank, S. and Hench, J. and Paulus, W. and Hasselblatt, M. and Hartmann, W. and Dohmen, H. and Keber, U. and Jank, P. and Denkert, C. and Stadelmann, C. and Bremmer, F. and Richter, A. and Wefers, A. and Ribbat-Idel, J. and Perner, S. and Idel, C. and Chiariotti, L. and Della Monica, R. and Marinelli, A. and Schüller, U. and Bockmayr, M. and Liu, J. and Lund, V.J. and Forster, M. and Lechner, M. and Lorenzo-Guerra, S.L. and Hermsen, M. and Johann, P.D. and Agaimy, A. and Seegerer, P. and Koch, A. and Heppner, F. and Pfister, S.M. and Jones, D.T.W. and Sill, M. and von Deimling, A. and Snuderl, M. and Müller, K.R. and Forgó, E. and Howitt, B.E. and Mertins, P. and Klauschen, F. and Capper, D. |
| Abstract: | The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs. |
| Keywords: | Carcinoma, DNA Helicases, DNA Methylation, Nuclear Proteins, Proteomics, Reproducibility of Results, Transcription Factors |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 13 |
| Number: | 1 |
| Page Range: | 7148 |
| Date: | 28 November 2022 |
| Official Publication: | https://doi.org/10.1038/s41467-022-34815-3 |
| PubMed: | View item in PubMed |
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