Nanopore Sequencing as a Cutting-Edge Technology for Medulloblastoma Classification.

Background: Medulloblastoma (MB) is one of the most prevalent embryonal malignant brain tumors. Current classification organizes these tumors into four molecular subgroups (WNT, SHH, Group 3, and Group 4 MB). Recently, a comprehensive classification has been established, identifying numerous subtypes, some of which exhibit a poor prognosis.

Medulloblastomas with pathogenic variants: A weakly penetrant syndrome with a restricted spectrum in a limited age window.

Background: pathogenic variants (PV) have been recently identified as the most frequent variants predisposing to Sonic Hedgehog (SHH) medulloblastomas (MB); however, guidelines are still lacking for genetic counseling in this new syndrome.

Methods: We retrospectively reviewed clinical and genetic data of a French series of 29 -mutated MB.

Results: All patients developed SHH-MB, with a biallelic inactivation of found in 24 tumors.

Regulation of primary cilia disassembly through HUWE1-mediated TTBK2 degradation plays a crucial role in cerebellar development and medulloblastoma growth.

Development of the cerebellum requires precise regulation of granule neuron progenitor (GNP) proliferation. Although it is known that primary cilia are necessary to support GNP proliferation, the exact molecular mechanism governing primary cilia dynamics within GNPs remains elusive. Here, we establish the pivotal roles for the centrosomal kinase TTBK2 (Tau tubulin kinase-2) and the E3 ubiquitin ligase HUWE1 in GNP proliferation.