This German group utilized DNA methylation and expression profiles to subtype AT/RTs into 3 separate subgroups – tyrisonase (TYR), sonic hedgehog (SHH), and MYC. These 3 subgroups are characterized by the active pathways in them as well as by the location of enhancers and the relative importance of different transcription factors. The finding of different activated elements in tumors that are generally mutationally quiet (other than SMARCB1) mutations may allow for more targeted therapies which the authors start to show with in-vitro apoptosis achieved using a MITF inhibitor in the TYR group.
* This study is part of the worldwide (unfortunately uncoordinated) effort to subgroup embryonal tumors in a manner parallel to the successful medulloblastoma classification. While this study seems convincing, it is not consistent with another study (Torchia et al., Lancet Oncology 2015) showing only 2 subgroups of AT/RT with different features. The degree of overlap between these two classification systems is yet to be seen.