Pediatric medulloblastoma - update on molecular classification driving targeted therapies

Abstract

As advances in the molecular and genetic profiling of pediatric medulloblastoma evolve, associations with prognosis and treatment are found (prognostic and predictive biomarkers) and research is directed at molecular therapies. Medulloblastoma typically affects young patients, where the implications of any treatment on the developing brain must be carefully considered. The aim of this article is to provide a clear comprehensible update on the role molecular profiling and subgroups in pediatric medulloblastoma as it is likely to contribute significantly toward prognostication. Knowledge of this classification is of particular interest because there are new molecular therapies targeting the Shh subgroup of medulloblastomas.

Keywords: classification; medulloblastoma; molecular; pediatric; therapies.

Figure 1

MRI of head showing sagittal and horizontal views. Sagittal view shows a midline posterior fossa medulloblastoma with intermediate signal intensity. There is an obstruction to the flow of CSF, marked hydrocephalus, and edema. Horizontal view shows a homogenous enhancing medulloblastoma arising from the right cerebellar hemisphere with displacement of the vermis.

Figure 2

Graph showing the age distribution for different subgroups of medulloblastoma adapted from Ref. (8).

Figure 3

Histology showing (A) Classic medulloblastoma with nuclear β-catenin immunostaining; (B) Nodular medulloblastoma with cytoplasmic β-catenin immunostaining; (C) Anaplastic medulloblastoma with cytoplasmic β-catenin immunostaining.

Figure 4

Schematic overviewing Wnt signaling.

Figure 5

Schematic overviewing Shh signaling.