Methylation profiling identifies distinct MPNST groups. (A) Unsupervised hierarchical clustering showing 309 samples from RNOH and Heidelberg clustered in epigenetically distinct subgroups of benign nerve sheath tumours, low‐grade MPNSTs, high‐grade MPNSTs, UPSs, epithelioid MPNSTs, and spindle cell rhabdomyosarcoma (SC‐RMS) subtypes. MPNSTs are clustered in methylation groups (MeGrps) 4 and 5. MeGrp 4 contains MPNSTs showing loss of H3K27me3 and hypermethylation of PRC2 pathway genes as opposed to MeGrp 5, which contains MPNST and UPS samples with retained H2K37me3 expression. The majority of the paraspinal tumours clustered in MeGrp 5. MeGrp 1 is composed largely of benign nerve sheath tumours and low‐grade MPNSTs. MeGrp 2 consists mostly of sarcoma NOS samples (not sequenced), whereas MeGrp 3 contains mostly SC‐RMS cases. MeGrp 6 contains the majority of epithelioid MPNSTs. (B) Pie chart showing the association between the MPNSTs in MeGrps 4 and 5 and the histopathological groups (HP Grps) 1A, 1B, and 2. The histopathology of the Heidelberg cases has not been reviewed in this study.