Genomic hallmarks and therapeutic implications of G0 cell cycle arrest in cancer.

ABSTRACT:

Background

Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown.

Results

We develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of

SUBMITTER: Wiecek AJ 

PROVIDER: S-EPMC10204193 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature