PNR-39: DISTINCT GENE FUSIONS SEGREGATE SUB-CLASSES OF CNS-PNETs

Primitive neuroectodermal brain tumours (PNETs) have dismal overall 20-40% survival. Clinical diagnosis of PNETs has proven challenging due to histological similarities to other tumours types. Our previous studies indicated at least 3 transcriptional sub-types of CNS-PNETs. To further define molecular features of CNS-PNETs that are distinct from other brain tumours, this study compared genetic and epigenetic profiles of 221 PNETs with that of 15 angiosarcomas, 162 atypical teratoid/rhabdoid tumours, 8 chondroblastomas, 29 liposarcomas, 48 ependymomas, 293 glioblastomas, 42 leiomyosarcomas, 377 low grade gliomas, 91 medulloblastomas, 9 malignant rhabdoid tumours, 34 neuroblastomas, 60 pleomorphic adenomas, 20 pineoblastomas, 10 sarcomas, 14 normal brain, and 27 fetal brain. Analyses included RNA and exome sequencing (n = 40), methylation, CNV (n = 1355), and gene expression profiling (n= 95), as well as targeted sequencing and Nanostring analyses for known alterations and fusions characteristic of other tumour types. To date these analyses reveal further segregation of CNS-PNETs into 4 epigenetic sub-types including Group 1 PNETs with the known C19MC OncomiR cluster. Groups 2 and 3 were respectively defined by gene-fusion events and elevated FOXR2 and BCOR expression, while group 4 was enriched for mesenchymal features. Integrated analyses indicate molecular sub-types of CNS-PNETs have distinct clinical and survival features.