Multi-omics approaches reveal that diffuse midline gliomas present altered DNA replication and are susceptible to replication stress therapy.

ABSTRACT:

Background

The fatal diffuse midline gliomas (DMG) are characterized by an undruggable H3K27M mutation in H3.1 or H3.3. K27M impairs normal development by stalling differentiation. The identification of targetable pathways remains very poorly explored. Toward this goal, we undertake a multi-omics approach to evaluate replication timing profiles, transcriptomics, and cell cycle features in DMG cells from both H3.1K27M and H3.3K27M subgroups and perform a comparative, integrative data analysis with healthy brain tissue.

Results

DMG cells present differential replication timing in each subgroup, which, in turn, correlates with significant differential gene expression. Differentially expressed genes in S phase are involved in various pathways related to DNA replication. We detec

SUBMITTER: Hains AE 

PROVIDER: S-EPMC11660928 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature