The Peter Pan Syndrome: Oncohistones Stall Development in Pediatric Cancers

CCR Grand Rounds Dr. Jabado ’ s research focuses on elucidating genetic signatures of pediatric astrocytomas and examining how they compare to adults. These are deadly brain tumors that originate in the brain and include glioblastomas (GBM, the highest grade of astrocytomas), which are one of the deadliest cancers in humans. Her group uncovered that pediatric high-grade astrocytomas (HGA) are molecularly and genetically distinct from adult tumors. They also identified a new molecular mechanism driving pediatric HGA, namely recurrent somatic driver mutations in the tail of histone 3 variants (H3.3 and H3.1). These mutations lead to amino acid substitutions at key residues and are tightly correlated with a distinct global DNA methylation pattern, neuroanatomical locations and age specificities. Dr. Jabado ’ s and her team ’ s research findings position them as leaders in the field of HGA, and at the forefront of significant breakthroughs for this deadly brain tumor. Ultimately, based on these findings, patients could be stratified based on their genetic/molecular signature, and assigned to a beneficial therapeutic strategy, bringing needed effective interventions in this devastating cancer. Additionally, Dr. Jabado and her colleagues established a TCGA-like initiative by creating the International CHildhood Astrocytoma INtegrated Genomic and Epigenomic (ICHANGE) Consortium. This is a unique set of resources which enables the scientific world to investigate astrocytomas in...
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