Failure of human rhombic lip differentiation underlies medulloblastoma formation.

ABSTRACT: Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain^1-4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage^5-8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL^9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage^3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in

SUBMITTER: Hendrikse LD 

PROVIDER: S-EPMC10026724 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature