High resolution DNA copy number analysis of supratentorial primitive neuroectodermal tumours indicates frequent alterations in the cadherin-catenin adhesion pathway

Supratentorial primitive neuroectodermal tumours (sPNET) are highly malignant pediatric brain tumours, but the events contributing to sPNET pathogenesis are not well described. I have utilized high resolution DNA copy number and gene expression analysis in order to map candidate disease genes and obtain a comprehensive characterization of the molecular aberrations present in sPNET. DNA copy number analysis of the largest collection to date (n=44) confirmed that sPNET are genetically distinct from other CNS PNET such as medulloblastoma. sPNET are genetically heterogeneous, and known and novel genes with copy number aberrations were identified. Focal genomic deletions and gene expression analysis indicated frequent deregulation of intercellular adhesion in sPNET. This thesis focused on the characterization of PTPRM. Preliminary experiments demonstrated an inhibition of cell growth in one PNET cell line but not the sPNET-derived cell line after PTPRM reconstitution, suggesting that PTPRM inhibition of PNET may be cell-type specific.