Genetically engineered cerebral organoids model brain tumor formation

Nat Methods. 2018 Aug;15(8):631-639. doi: 10.1038/s41592-018-0070-7. Epub 2018 Jul 23.


Brain tumors are among the most lethal and devastating cancers. Their study is limited by genetic heterogeneity and the incompleteness of available laboratory models. Three-dimensional organoid culture models offer innovative possibilities for the modeling of human disease. Here we establish a 3D in vitro model called a neoplastic cerebral organoid (neoCOR), in which we recapitulate brain tumorigenesis by introducing oncogenic mutations in cerebral organoids via transposon- and CRISPR-Cas9-mediated mutagenesis. By screening clinically relevant mutations identified in cancer genome projects, we defined mutation combinations that result in glioblastoma-like and central nervous system primitive neuroectodermal tumor (CNS-PNET)-like neoplasms. We demonstrate that neoCORs are suitable for use in investigations of aspects of tumor biology such as invasiveness, and for evaluation of drug effects in the context of specific DNA aberrations. NeoCORs will provide a valuable complement to the current basic and preclinical models used to study brain tumor biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology*
  • Disease Models, Animal
  • Genes, myc
  • Genetic Engineering
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Heterografts
  • Human Embryonic Stem Cells
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Mutation
  • Neuroectodermal Tumors, Primitive / genetics
  • Neuroectodermal Tumors, Primitive / pathology
  • Oncogenes
  • Organoids / pathology*
  • Transcriptome
  • Xenograft Model Antitumor Assays