Medulloblastomas in adults: prognostic factors and lessons from paediatrics

Curr Opin Neurol. 2011 Dec;24(6):626-32. doi: 10.1097/WCO.0b013e32834cd4b1.

Abstract

Purpose of review: Medulloblastomas are very rare in adults. Usual treatment consists of craniospinal radiation with or without chemotherapy. Current efforts focus on a better understanding of tumour biology, stratifying patients into risk groups and adapting treatment accordingly. This review discusses clinical and new molecular risk factors that will help to optimize treatment in adult medulloblastoma patients.

Recent findings: The clinical risk stratification should be complemented with new molecular prognostic markers. Gene-expression profiling has permitted identification of four to six molecular medulloblastoma subgroups. The WNT subgroup shows overexpression of genes of the WNT/wingless signalling pathway with frequent mutations of the CNNTB1 gene, loss of chromosome 6 and accumulation of nuclear β-catenin, and is most often seen in children with medulloblastomas of classical histology. This variant has a good prognosis. Activation of the sonic hedgehog pathway with frequent mutations of the PTCH and SUFU genes, loss of 9q, and positivity for GLI1 and SFRP1 is more frequent in children less than 3 years old and in adults, commonly associated with desmoplastic histology. Other subgroups are not so well defined and have overlapping characteristics, but MYC/MYCN amplification, 17q gain and, large cell/anaplastic histology are factors of poor prognosis.

Summary: New molecular subgroups will help tailor treatment and further develop new targeted therapies. Prospective and ideally randomized trials should be performed in adults, including risk stratification by molecular markers, to identify optimal treatment for each risk group.

Publication types

  • Review

MeSH terms

  • Adult
  • Biomarkers, Tumor
  • Child
  • Child, Preschool
  • Gene Expression Profiling
  • Humans
  • Medulloblastoma / classification
  • Medulloblastoma / genetics*
  • Medulloblastoma / pathology
  • Medulloblastoma / therapy*
  • Prognosis
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / physiology
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Biomarkers, Tumor
  • Wnt Proteins
  • beta Catenin