Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
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Background: Atypical teratoid rhabdoid tumor (ATRT) is the most common malignant brain tumor in infants, and more than 60% of children with ATRT die from their tumor. ATRT is associated with mutational inactivation/deletion of , a member of the SWI/SNF chromatin remodeling complex, suggesting that epigenetic events play a critical role in tumor development and progression. Moreover, disruption of SWI/SNF allows unopposed activity of epigenetic repressors, which contribute to tumorigenicity.
View Article and Find Full Text PDFPediatric skull base tumors: Clinical features and surgical outcomes; a single center retrospective study with a review of literature.
Brain Spine
November 2024
Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.
Article Synopsis
- Pediatric intracranial tumors at the skull base are rare, challenging to treat due to complex anatomy, and lack substantial clinical evidence, prompting a study on surgical approaches and outcomes.
- The study involved 12 children under 18 who underwent skull base surgery from 2017 to 2023, analyzing demographics, tumor details, surgical methods, and survival rates.
- Results indicated a predominance of female patients, varying tumor locations and types, with 58.3% achieving gross or near-total resection; however, 33.3% of patients died from tumor progression within an average of 15 months.
Atypical teratoid/rhabdoid tumors (AT/RTs) of the central nervous system (CNS) are rare and aggressive, typically occurring in early childhood or infancy, with adult cases being extremely rare. These tumors are associated with the inactivation of the integrase interactor 1 (INI1) gene. The prognosis is poor, worsening significantly if metastasis is detected at diagnosis.
View Article and Find Full Text PDFDesigning a Time-Dependent Therapeutic Strategy using CDK4/6 Inhibitors in an Intracranial ATRT Model.
Neuro Oncol
December 2024
Department of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Background: Inhibitors targeting cyclin-dependent kinases 4 and 6 (CDK4/6), crucial for cell cycle regulation, have shown promise in early-stage studies for treating central nervous system (CNS) tumors. However, challenges such as limited CNS penetration, optimal treatment duration, and systemic side effects have impeded their clinical translation for pediatric brain tumors (PBTs).
Methods: We evaluated the potency of CDK4/6 inhibitors across various PBTs cell lines, focusing particularly on palbociclib against atypical teratoid rhabdoid tumor (ATRT) with cell viability assays and gene expression analysis.
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