title: The molecular classification of medulloblastoma:  driving the next generation clinical trials.
abstract: OBJECTIVE
  Most children diagnosed with cancer today are expected to be cured. Medulloblastoma, the most common pediatric malignant brain tumor, is an example of a disease that has benefitted from advances in diagnostic imaging, surgical techniques, radiation therapy and combination chemotherapy over the past decades. It was an incurable disease 50 years ago, but approximately 70% of children with medulloblastoma are now cured of their disease. However, the pace of increasing the cure rate has slowed over the past 2 decades, and we have likely reached the maximal benefit that can be achieved with cytotoxic therapy and clinical risk stratification. Long-term toxicity of therapy also remains significant. To increase cure rates and decrease long-term toxicity, there is great interest in incorporating biologic 'targeted' therapy into treatment of medulloblastoma, but this will require a paradigm shift in how we classify and study disease.
  
  
  RESULTS
  Using genome-based high-throughput analytic techniques, several groups have independently reported methods of molecular classification of medulloblastoma within the past year. This has resulted in a working consensus to view medulloblastoma as four molecular subtypes, including wingless-type murine mammary tumor virus integration site (WNT) pathway subtype, Sonic Hedgehog pathway subtype and two less well defined subtypes (groups C and D).
  
  
  CONCLUSIONS
  Novel classification and risk stratification based on biologic subtypes of disease will form the basis of further study in medulloblastoma and identify specific subtypes that warrant greater research focus.
authors.affiliation: Seattle Children's Hospital, University of Washington School of Medicine, Washington, USA. sarah.leary@seattlechildrens.org
authors.forename: Sarah E S
authors.initials: SE
authors.lastname: Leary
authors.forename: James M
authors.initials: JM
authors.lastname: Olson
mesh_terms: D001932:Brain Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D004273:DNA, Neoplasm; D012334:RNA, Neoplasm