Genetic and molecular alterations across medulloblastoma subgroups

J Mol Med (Berl). 2015 Oct;93(10):1075-84. doi: 10.1007/s00109-015-1333-8. Epub 2015 Sep 9.

Abstract

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.

Keywords: Medulloblastoma; Molecular genetics; Subgroups; Therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Genetic Predisposition to Disease
  • Hedgehog Proteins / genetics
  • Humans
  • Medulloblastoma* / drug therapy
  • Medulloblastoma* / genetics
  • Medulloblastoma* / pathology
  • Wnt Proteins / genetics

Substances

  • Antineoplastic Agents
  • Hedgehog Proteins
  • SHH protein, human
  • Wnt Proteins