Researchers from the Aqeilan Lab, in collaboration with the Drier Lab at the Lautenberg Center for Immunology and Cancer Research, have uncovered new insights into how inherited BRCA1 and BRCA2 mutations initiate cancer development long before tumors form. In a study published in Cell Death & Disease, the team mapped DNA double-strand breaks across the genome of breast cells from women carrying BRCA mutations, revealing early and widespread genomic instability in otherwise normal tissue.
Using advanced genome-wide “breakome” profiling, the researchers show that BRCA-mutant cells accumulate DNA breaks preferentially in highly active genes and cancer-related pathways, mirroring patterns seen in established breast tumors. These findings suggest that cancer predisposition in BRCA mutation carriers begins far earlier than previously appreciated, driven by transcription-associated DNA damage and impaired repair mechanisms.
The study, led by PhD student Sara Oster Flayshman with senior authors Prof. Rami Aqeilan and Prof. Yotam Drier, provides new mechanistic insight into how inherited defects in DNA repair prime cells for malignant transformation. Beyond deepening our understanding of cancer initiation, this work opens new avenues for early detection and prevention strategies in individuals at high genetic risk.
