Structural variant and nucleosome occupancy dynamics postchemotherapy in a HER2+ breast cancer organoid model.

ABSTRACT: The most common chemotherapeutics induce DNA damage to eradicate cancer cells, yet defective DNA repair can propagate mutations, instigating therapy resistance and secondary malignancies. Structural variants (SVs), arising from copy-number-imbalanced and -balanced DNA rearrangements, are a major driver of tumor evolution, yet understudied posttherapy. Here, we adapted single-cell template-strand sequencing (Strand-seq) to a HER2+ breast cancer model to investigate the formation of doxorubicin-induced de novo SVs. We coupled this approach with nucleosome occupancy (NO) measurements obtained from the same single cell to enable simultaneous SV detection and cell-type classification. Using organoids from TetO-CMYC/TetO-Neu/MMTV-rtTA mice modeling HER2+ breast cancer, we generated 459 Strand-se

SUBMITTER: Starostecka M 

PROVIDER: S-EPMC11892646 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature