APOBEC3 mutagenesis drives therapy resistance in breast cancer.

ABSTRACT: Acquired genetic alterations drive resistance to endocrine and targeted therapies in metastatic breast cancer; however, the underlying processes engendering these alterations are largely uncharacterized. To identify the underlying mutational processes, we utilized a clinically annotated cohort of 3,880 patient samples with tumor-normal sequencing. Mutational signatures associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) enzymes were prevalent and enriched in post-treatment hormone receptor-positive cancers. These signatures correlated with shorter progression-free survival on antiestrogen plus CDK4/6 inhibitor therapy in hormone receptor-positive metastatic breast cancer. Whole-genome sequencing of breast cancer models and paired primary-metastatic s

SUBMITTER: Gupta A 

PROVIDER: S-EPMC12165862 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature