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• W2617029719 abstract "AbstractPreviously, we have identified nine distinct molecular groups of ependymoma across all age groups, three in each major anatomical compartment of the CNS: spinal, posterior fossa, and supratentorial. These nine molecular groups are genetically, epigenetically, transcriptionally, demographically, and clinically distinct. Pediatric intracranial ependymomas are either affiliated with the RELA and YAP1 supratentorial groups or with the posterior fossa PFA group. RELA and YAP1 ependymomas harbor recurrent and distinct fusion genes that drive the disease, but PFA ependymomas lack significant recurrent mutations, and the specific oncogenic events underlying these tumors remain undefined. Observing distinct outcomes among children with PFA ependymomas, we tested the hypothesis that further molecular diversity with clinical utility, including possible novel genetic alterations, may exist among these tumors. Genome-wide DNA methylation profiles of 681 pediatric PFA ependymomas were analyzed by unsupervised consensus hierarchical clustering and t-distributed stochastic neighbor embedding (tsne), which identified not only three major distinct molecular subgroups of PFA ependymoma: PFA-1, PFA-2, and PFA-3, but additional small subgroups that segregate within PFA-1 and PFA-2. Subgroups were characterized by distinct clinical and genetic characteristics; most PFA-3 tumors harbored 1q gain and occurred in children significantly older than those with PFA-1 and PFA-2 tumors. Some of the small subgroups demonstrated distinctive copy number alterations or gene mutations, e.g. H3 K27M. Outcome data revealed considerable heterogeneity among the different subgroups, overall survival at 5 years was >90% for one subgroup, but <20% for two others. We conclude that further molecular refinement of pediatric PFA ependymomas has clinical utility and the potential for enhanced risk assessment or therapeutic stratification. In addition, identification of PFA subgroups and further molecular heterogeneity within these subgroups may help to identify the drivers of PFA ependymomas." @default.
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• W2617029719 date "2017-05-31" @default.
• W2617029719 modified "2023-09-26" @default.
• W2617029719 title "EPND-07. MOLECULAR HETEROGENEITY AMONG PEDIATRIC POSTERIOR FOSSA EPENDYMOMA" @default.
• W2617029719 doi "https://doi.org/10.1093/neuonc/nox083.065" @default.
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