UCLA

Abstract Rhabdoid tumor predisposition syndrome 1 (RTPS1) results from inactivation of the tumor-suppressor SMARCB1, a core component of the BAF (hSWI/SNF) complex. Rhabdoid tumors (RTs) are a highly malignant group of neoplasms that usually occur in children less than 2 years of age, which have no effective medical treatment. We discovered that the myelin protein zero (P0) gene serves as a lineage marker to trace the developmental origin of RT neoplastic cells. Ablating Smarcb1 in the P0+early neural crest lineage was necessary and sufficient to initiate tumorigenesis in cranial nerves and meninges, faithfully recapitulating histological features and molecular profiles of human RTs. About 65% of P0-CreC;Smarcb1flox/floxmice developed tumors between 1.5 and 5 months of age with an overall median survival of 3.2 months. These mice developed aggressive tumors emanating from cranial nerves, meninges, with variable extent of brain invasion, and spinal nerve roots. This genetically engineered mouse model opens the doors for deciphering the origin and evolution of RTs to identify effective therapies.