Table 1.

Generation of primary brain tumors in GEM similar to and based on genetic alterations found in the human brain tumors

Tumor classificationPathway/geneInitial genetic alteration by vectorTissue-specific promoterReference
Low-grade (WHO grade 2) astrocytomaRasGainGFAP24
Nf1+p53Loss29
SrcGainGFAP22
Anaplastic (WHO grade 3) astrocytomaRasGainGFAP24
Nf1 + p53Loss29
SrcGainGFAP22
Rb inactivated by SV40 large T antigenGFAP62
GBM (WHO grade 4) astrocytomaRas + AktGainNestin37
PDGFBGainMixed18
Nf1 + p53Loss29
Ink4aArf + RasLoss/gainGFAP/Nestin63
Low-grade (WHO grade 2) oligodendrogliomaArfLoss64
PDGFBGainNestin65
v-erbBGainS100β27
Ras + EGFRVIIIGainGFAP28
Anaplastic (WHO grade 3) oligodendrogliomaInk4aArf + PDGFBLoss/gainNestin65
Mixed glioma (oligoastrocytoma)Ink4aArf + PDGFBLoss/gainGFAP65
MedulloblastomaPtchLoss66
67
68
Ptch + p53Loss70
Rb + p53LossGFAP32
ShhGainCerebellar progenitors69
Shh + mycGainNestin71
Lig4 + p53Loss72
Parp + p53Loss73
SmoA1GainND233
Shh + Akt or IGF2GainNestin31
  • NOTE: Tumor cells of origin are unknown in the knockout GEMs; promoters used for somatic cell gene transfer or limiting transgene expression are listed and correspond to glioneuronal progenitor cells (nestin, S100β), differentiated astrocytes (GFAP), or the external granule layer progenitor cells (ND2).