G-quadruplexes as a source of vulnerability in BRCA2<i>-</i>deficient granule cell progenitors and medulloblastoma.

ABSTRACT: Biallelic pathogenic variants in the essential DNA repair gene BRCA2 cause Fanconi anemia complementation group D1. Patients in this group are highly prone to develop embryonal tumors, most commonly medulloblastoma arising from the cerebellar granule cell progenitors (GCPs). GCPs undergo high proliferation in the postnatal cerebellum under Sonic Hedgehog (SHH) activation, but the type of DNA lesions that require the function of the BRCA2 to prevent tumorigenesis remains unknown. To identify such lesions, we assessed both GCP neurodevelopment and tumor formation using a mouse model with deletion of exons three and four of Brca2 in the central nervous system, coupled with global Trp53 loss. Brca2^Δex3-4;Trp53^-/- animals developed SHH subgroup

SUBMITTER: Keahi DL 

PROVIDER: S-EPMC12415258 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature