Quantifying replication stress in cancer without proliferation confounding.

ABSTRACT: Replication stress (RS) is a major driver of genomic instability and cancer development through impaired DNA replication that can lead to chromosomal instability (CIN). Although RS is mechanistically linked to CIN, its relationship with cellular proliferation is complex. Depending on the context, RS can either promote or suppress cell growth. Existing RS gene expression signatures overlook this complexity, relying on the overexpression of oncogenes such as MYC, which introduces a proliferation bias. To disentangle genuine RS from confounding cell cycle and proliferation transcriptional profiles, we developed and validated a novel gene expression signature that accurately predicts RS independently of oncogene activity. This tumorigenic RS signature (TRSS) captures RS-related transcri

SUBMITTER: Jungk P 

PROVIDER: S-EPMC12632277 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature