LAUSR

2028Background: Pineoblastoma (PB) is a rare but aggressive pediatric brain tumour arising from the pineal gland. Overall survival rates are estimated at 50-60%, with younger patients ( < 5 years old) faring much worse (15-40%) despite intensive treatment regimens. Although germline RB1 and DICER1 alterations have been reported in a small proportion of PB, the clinical significance of such alterations and the biology of sporadic cases remains unknown. Methods: We collected tumor tissue from 75 cases of PB diagnosed at their local centres from across five continents. We undertook global DNA methylation profiling and performed multiple orthogonal consensus clustering analyses to elucidate PB subgroups. Chromosomal copy number alterations were determined using Conumee then GISTIC 2.0. Mutational analysis was conducted by whole exome and RNA sequencing. Clinical data was analyzed with correlative statistical methods and outcomes were measured by Kaplan-Meier survival estimates. Results: We discovered that PBs...