Glioblastoma exhibits marked biological heterogeneity that varies with patient age, reflecting differences in cellular origin, epigenetic state, and tumor evolution. DNA methyltransferase 3B (DNMT3B), a key mediator of de novo DNA methylation during embryonic development, is aberrantly expressed in multiple cancers, including glioblastoma, where its function may diverge between regulating developmental programs and sustaining uncontrolled proliferation. Pediatric and adult glioblastomas differ substantially in their epigenomic landscapes, suggesting that DNMT3B expression may reflect age-dependent contexts such as neural progenitor maintenance in younger patients versus proliferation-associated epigenetic dysregulation in adults. Understanding whether DNMT3B activity in glioblastoma aligns more closely with developmental lineage programs or with cell-cycle–driven tumor expansion across age strata is essential for clarifying its biological role and therapeutic relevance.
