Although the inactivation of p53 alone was not required for the tumor initiation, D22 TPCs harboring TP53R248Q in combination with BRAFV600E or NRASQ61R generated undifferentiated tumors with a pleomorphic and undifferentiated morphology recapitulating the heterogeneity and the phenotypic characteristics of ATC, expressing low levels of Tg, CK19 and NIS as compared with the well-differentiated TC histotypes (Fig. 1F, G and Supplementary Fig. 2e). The gene discussed is TG; the disease is neoplasm.