Chromosomal instability drives ECM remodelling and drug vulnerabilities in the first Afro-Caribbean breast cancer cell lines

Women of African ancestry develop more aggressive breast cancer (BCa) with poorer survival outcomes, yet only 8% of available cell lines represent this population, impeding targeted treatment development. Here, we aimed to establish and characterize new cell lines from an Afro-Caribbean patient to better understand population-specific BCa biology. We developed three lines (ACRJ-BC24 parent, α, and β) from a patient with 100% African ancestry. Karyotype analysis revealed progressive chromosomal instability, with the β-clone showing X-11 translocations correlating with higher Ki-67 expression and enhanced tumorigenic capacity. Immunohistochemistry and immunoblotting demonstrated their transition from hormone-positive to triple-negative phenotypes. Transcriptional profiling identified significant enrichment in extracellular matrix organization pathways mechanistically linked to chromosomal instability, explaining their distinct drug responses. The β-clone's enhanced sensitivity to PARP inhibitors correlates with its chromosomal abnormalities, while the parent line's sensitivity to gemcitabine possibly relates to ECM-mediated nucleoside transporter regulation. These lines provide valuable tools for studying BCa disparities.