Multi-omics dissection of MAPK-driven senescence unveils therapeutic vulnerabilities in KIAA1549::BRAF-fusion pediatric low-grade glioma models.

ABSTRACT: Pilocytic astrocytomas (PA), the most common pediatric low-grade gliomas (pLGGs), are characterized by genetic MAPK pathway alterations leading to constitutive activation and oncogene-induced senescence (OIS) accompanied with the senescence-associated secretory phenotype (SASP). This study investigates the molecular mechanisms of signaling pathways regulating OIS and SASP in pLGGs using a multi-omics approach. We utilized senescent DKFZ-BT66 cells derived from a primary KIAA1549::BRAF-fusion positive PA to generate RNA-sequencing and phospho-/proteomic datasets before and after treatment with the MEK inhibitor trametinib. Multi-omics factor analysis (MEFISTO) and single sample gene set enrichment analysis (ssGSEA) were employed to identify key OIS effectors and differentially regulated pat

SUBMITTER: Sigaud R 

PROVIDER: S-EPMC12185702 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature