Modeling human cancer using LEGO organoid

To systematically model the genetic spectrum that are affected in human GBM, we use human iPSC-derived organoid to dissect the genetic heterogeneity in GBM. Using CRISPR/Cas9, we generated a spectrum of mutation combinations (Pten, Trp53, Cdkn2a, Cdkn2b, Nf1, Rb1, Egfr, Tert etc.), which are the most frequently mutated genes in human GBM (McLendon et al., 2008), in human iPSCs. We could induce GBM organoid from these cells, the GBM organoid (LEGO: Laboratory Engineered Glioma Organoid) derived from these cells recapitulate key molecular features of human GBM. We are using LEGO models to dissect the interaction between genetic heterogeneity and functional heterogeneity in GBM. Drug screen are also being conducted to build a genotype-based drug reference for personalized treatment of GBM.