Figure 5.

Phenotypic heterogeneity of glioblastoma may result from genotypic heterogeneity associated with a different number of extrachromosomal amplicons and their different composition. Various types of tumor initiating cells can convert/transit from one type to another or to non-TIC cells, whereas non-TIC cells can convert/transit to TIC due to the changes in types of amplicons as well as their numbers and epigenetic changes. The presence of different TIC increases tumor aggressiveness, since neoplastic cells are able to invade different environments and survive many environmental changes including applied therapy. Amplicons can be transported in extracellular vesicles. Separated amplicons contain genes such as EGFR and EGFRvIII, MDM2, PDGFR, or c-MYC.