Genetic and molecular alterations across medulloblastoma subgroups.
Medulloblastoma is the most common malignant brain tumour diagnosed in children. Over the last few decades, advances in radiation and chemotherapy have significantly improved the odds of survival. Nevertheless, one third of all patients still succumb to their disease, and many long-term survivors are afflicted with neurocognitive sequelae. Large-scale multi-institutional efforts have provided insight into the transcriptional and genetic landscape of medulloblastoma. Four distinct subgroups of medulloblastoma have been identified, defined by distinct transcriptomes, genetics, demographics and outcomes. Integrated genomic profiling of each of these subgroups has revealed distinct genetic alterations, driving pathways and in some instances cells of origin. In this review, we highlight, in a subgroup-specific manner, our current knowledge of the genetic and molecular alterations in medulloblastoma and underscore the possible avenues for future therapeutic intervention.
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Patryk
P
Skowron
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.|Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Vijay
V
Ramaswamy
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada. mdtaylor@sickkids.ca.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. mdtaylor@sickkids.ca.|Division of Neurosurgery, The Hospital for Sick Children, 555, University Avenue, Toronto, Ontario, M5G 1X8, Canada. mdtaylor@sickkids.ca.
Michael D
MD
Taylor
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D051153:Wnt Proteins / Q000235:genetics
D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; C509239:SHH protein, human; D051153:Wnt Proteins
Medulloblastoma; Molecular genetics; Subgroups; Therapy