Gliomas are the most common malignancies of the central nervous system (CNS). A significant proportion of both low- and high-grade gliomas in children, adolescents, and young adults have specific genetic events which can be traced to the germline. Despite integration of genomic findings in recent CNS tumor classifications, germline origins of these genetic events are seldom highlighted. These cancer predisposition syndromes can predispose the individual and family members to multiple cancers in different organs beyond the CNS and to other non-oncologic manifestations caused by the genetic dysfunction. Recent molecular discoveries and careful surveillance have resulted in improved survival and reduced morbidity for many of these conditions. Importantly, identifying a genetic predisposition can alter treatment of the existing malignancy, by mandating the use of a different protocol, targeted therapy, or other novel therapies. Hence, prompt diagnosis is sometimes crucial for these young patients. High index of suspicion and early referral to genetic testing and counseling are important and may be beneficial to these families. In this review, we discuss the clinical manifestations, genetics, tumor management, and surveillance in these patients. These provide insights into the complex mechanisms in glioma-genesis that can impact the treatment and survival for these patients and families in the future.

Ependymomas are a lethal central nervous system (CNS) tumor found in both adults and children. Recent efforts have focused on risk stratification by classifying the molecular variants of CNS ependymoma. Despite this increased knowledge of molecular drivers, much less is known about the metabolism of these subgroups. Disruption of cellular metabolism can drive the transition of normal neuronal cells to tumor cells. A shift from anaerobic to aerobic metabolism as the primary energy source is a hallmark of cancer, promoting cancer cell proliferation, and avoidance of cellular apoptotic cues. This review aims to discuss the current knowledge regarding metabolism in ependymoma cells compared to normal brain cells and the implications of metabolic changes with regard to tumorigenesis, the tumor microenvironment, and possible targets for treatment.

Medulloblastoma is a major cause of cancer-related morbidity and mortality in children, as a significant proportion of patients succumb to their disease and most survivors are left with life-long sequelae of therapy. Prior medulloblastoma classification systems relied heavily on histology and failed to account for tumor biology. The upcoming 2021 WHO classification of central nervous system tumors now firmly establishes that medulloblastoma actually comprises at least four distinct molecular entities, with considerable substructure within each group. For the first time, the study design of contemporary clinical trials has now recognized the molecular heterogeneity of medulloblastoma. The incorporation of routine molecular subgrouping into upcoming clinical trials has the potential to significantly improve survival and quality of life for children and adults diagnosed with medulloblastoma. This review was conducted to summarize these recent advances in the genomics of medulloblastoma and to summarize the timely results of molecularly-informed published clinical trials. Specifically, English language literature will be reviewed in addition to the results of SJMB03, ACNS0331, and ACNS0332.