Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study

AbstractPineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1,DROSHA, andDGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenicMYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized byRB1 loss with gain ofmiR-17/92, and recurrent gain or amplification ofMYC. PB sub-groups exhibited distinct clinical features: group 1 –3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were...
Source: Acta Neuropathologica - Category: Neurology Source Type: research