Atypical teratoid rhabdoid tumors (ATRT) are rare and fast-growing cancers of the brain and spinal cord. About half of ATRTs begin in the cerebellum or brain stem and usually strike children three years or younger. The cancer is primarily linked to inactivation of a gene called SMARCB1, a subunit of the BAF complex, which helps regulate gene expression in developmental processes by remodeling chromatin (the collective term for DNA and its protein packaging). In a September paper in Genes & Development, a team led by Ludwig San Diego’s Frank Furnari described how the loss of the tumor suppressor gene SMARCB1 affects neural development. The researchers engineered human induced pluripotent stem cells to lose SMARCB1 on demand and studied the effects of that loss on the differentiation of the cells into either neurons or cerebral organoids—cultured mimics of brain tissue. Frank and his team identified an interaction between SMARCB1 loss and neural differentiation pressure that causes a resistance to terminal differentiation and a defect in maintaining a normal cell state, which resembled that observed in ATRT. The researchers plan to use their model to identify drug targets that restore normal neural development to treat the cancer.
This article appeared in the December 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).