Gene expression analysis of human medulloblastoma and neural stem cells

Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified – WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. The gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Total RNAwas extracted from 19 human primary medulloblastoma specimens, one human normal fetal brain (NFB) sample consisting of total RNA pooled from 50 individuals (embryonic week 22-33), two normal human fetal germinal matrix (NFGM) samples obtained from the lateral sub-ventricular zones of two 16 week old male fetuses, and CD133+ neural stem cells and CD133- neural progenitor cells isolated from embryonic stem cell derived neurospheres from three individuals. Gene expression profiling was carried out using Affymetrix U133A genechips.