Tumor organoids were genetically engineered from normal colonic organoids to harbor mutations in Apc, Tp53 and Kras loci (ApcΔ/Δ, KrasG12D, Tp53Δ/Δ; AKP) and either transplanted directly into syngeneic mice, or re-cultured upon one round of orthotopic growth to promote further tumor progression in vivo (AKPre). Here, TP53 is linked to neoplasm.