Cody L Nesvick1, Lucie Lafay-Cousin2, Aditya Raghunathan3, Eric Bouffet4,5, Annie A Huang4,5, David J Daniels6. 1. Department of Neurological Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA. 2. Departments of Oncology and Paediatrics, Alberta Children's Hospital Research Institute at the University of Calgary, Calgary, AB, Canada. 3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 4. Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada. 5. 5Department of Paediatrics, University of Toronto, Toronto, ON, Canada. 6. Department of Neurological Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA. daniels.david@mayo.edu.
Abstract
INTRODUCTION: Atypical teratoid rhabdoid tumor (ATRT) is a rare, often lethal brain tumor of childhood characterized by a complex epigenetic landscape amongst a simple genetic background. Recent molecular studies have defined key biologic events that contribute to tumorigenesis and molecular subtypes of ATRT. METHODS: Seminal studies on ATRT are reviewed with an emphasis on molecular pathogenesis and its relevance to novel therapeutics. RESULTS: In this review, we summarize the key clinicopathologic and molecular features of ATRT, completed and ongoing clinical trials and outline the translational potential of novel insights into the molecular pathogenesis of this tumor. CONCLUSIONS: SMARCB1 loss is the key genetic event in ATRT pathogenesis that leads to widespread epigenetic dysregulation and loss of lineage-specific enhancers. Current work is defining subtype-specific treatments that target underlying molecular derangements that drive tumorigenesis.
INTRODUCTION: Atypical teratoid rhabdoid tumor (ATRT) is a rare, often lethal brain tumor of childhood characterized by a complex epigenetic landscape amongst a simple genetic background. Recent molecular studies have defined key biologic events that contribute to tumorigenesis and molecular subtypes of ATRT. METHODS: Seminal studies on ATRT are reviewed with an emphasis on molecular pathogenesis and its relevance to novel therapeutics. RESULTS: In this review, we summarize the key clinicopathologic and molecular features of ATRT, completed and ongoing clinical trials and outline the translational potential of novel insights into the molecular pathogenesis of this tumor. CONCLUSIONS: SMARCB1 loss is the key genetic event in ATRT pathogenesis that leads to widespread epigenetic dysregulation and loss of lineage-specific enhancers. Current work is defining subtype-specific treatments that target underlying molecular derangements that drive tumorigenesis.
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