Molecular genetics of paediatric brain tumours and opportunities for precision medicine - a focus on infant tumours

Curr Opin Neurol. 2022 Dec 1;35(6):772-778. doi: 10.1097/WCO.0000000000001110. Epub 2022 Oct 4.


Purpose of review: The last few decades have seen an explosion in our understanding of the molecular drivers of childhood brain tumours. These insights have opened the possibility for precision medicine approaches for some tumour types. However, a different spectrum of tumours is more likely to occur in infants and young children, who face additional therapeutic challenges. This review focuses on recent advances in molecular genetics of common infant brain tumours and their implication for diagnosis, prognostication and utilization of precision oncology approaches.

Recent findings: Infant tumours have different biology and outcomes than similar tumours in older children and adults. For low-grade gliomas, targeted MAPK inhibition is well tolerated and likely efficacious. In high-grade gliomas, common tyrosine kinase alterations offer compelling targets for inhibition that are currently being evaluated. Paediatric-specific sequencing and methylation analysis offer insights into the driving biology of infant medulloblastoma, atypical teratoid rhabdoid tumours, embryonal tumours with multilayered rosettes, ependymoma and choroid plexus tumours, with molecular subgrouping shedding insights into distinct driving biology and clinical outcomes.

Summary: Infant brain tumours are rare and heterogenous, with overall poor outcomes. Advances in molecular genetics have been incorporated into their diagnostic criteria and allow for accurate subgrouping and improved prognostication. The utilization of targeted agents appears beneficial for many low-grade gliomas and a subset of high-grade gliomas, but further research is urgently needed to improve outcomes for other tumour entities.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / therapy
  • Cerebellar Neoplasms*
  • Child
  • Child, Preschool
  • Glioma* / pathology
  • Humans
  • Infant
  • Molecular Biology
  • Precision Medicine