Direct genetic transformation bypasses tumor-associated DNA methylation alterations.

ABSTRACT:

Background

Tumors represent dynamically evolving populations of mutant cells, and many advances have been made in understanding the biology of their progression. However, there are key unresolved questions about the conditions that support a cell's initial transformation, which cannot be easily captured in patient populations and are instead modeled using transgenic cellular or animal systems.

Results

Here, we use extensive patient atlas data to define common features of the tumor DNA methylation landscape as they compare to healthy human cells and apply this benchmark to evaluate 21 engineered human and mouse models for their ability to reproduce these patterns. Notably, we find that genetically induced cellular transformation rarely recapitulates the widespread de novo met

SUBMITTER: Hetzel S 

PROVIDER: S-EPMC12273271 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature