TY - JOUR AU - Jurmeister, Philipp AU - Glöß, Stefanie AU - Roller, Renée Fabienne AU - Leitheiser, Maximilian AU - Schmid, Simone AU - Mochmann, Liliana H AU - Payá Capilla, Emma AU - Fritz, Rebecca AU - Dittmayer, Carsten AU - Friedrich, Corinna AU - Thieme, Anne AU - Keyl, Philipp AU - Jarosch, Armin AU - Schallenberg, Simon AU - Bläker, Hendrik AU - Hoffmann, Inga AU - Vollbrecht, Claudia AU - Lehmann, Annika AU - Hummel, Michael AU - Heim, Daniel AU - Haji, Mohamed AU - Harter, Patrick AU - Englert, Benjamin AU - Frank, Stephan AU - Hench, Jürgen AU - Paulus, Werner AU - Hasselblatt, Martin AU - Hartmann, Wolfgang AU - Dohmen, Hildegard AU - Keber, Ursula AU - Jank, Paul AU - Denkert, Carsten AU - Stadelmann, Christine AU - Bremmer, Felix AU - Richter, Annika AU - Wefers, Annika AU - Ribbat-Idel, Julika AU - Perner, Sven AU - Idel, Christian AU - Chiariotti, Lorenzo AU - Della Monica, Rosa AU - Marinelli, Alfredo AU - Schüller, Ulrich AU - Bockmayr, Michael AU - Liu, Jacklyn AU - Lund, Valerie J AU - Forster, Martin AU - Lechner, Matt AU - Lorenzo-Guerra, Sara L AU - Hermsen, Mario AU - Johann, Pascal D AU - Agaimy, Abbas AU - Seegerer, Philipp AU - Koch, Arend AU - Heppner, Frank AU - Pfister, Stefan AU - Jones, David AU - Sill, Martin AU - von Deimling, Andreas AU - Snuderl, Matija AU - Müller, Klaus-Robert AU - Forgó, Erna AU - Howitt, Brooke E AU - Mertins, Philipp AU - Klauschen, Frederick AU - Capper, David TI - DNA methylation-based classification of sinonasal tumors. JO - Nature Communications VL - 13 IS - 1 SN - 2041-1723 CY - [London] PB - Nature Publishing Group UK M1 - DKFZ-2022-02939 SP - 7148 PY - 2022 AB - 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. LB - PUB:(DE-HGF)16 C6 - pmid:36443295 DO - DOI:10.1038/s41467-022-34815-3 UR - https://inrepo02.dkfz.de/record/182807 ER -