homologous recombination deficiency
A genomic phenotype characterized by impaired DNA double-strand break repair, creating vulnerability to PARP inhibitors.
Full Definition
Homologous recombination deficiency (HRD) occurs when cells cannot properly repair DNA double-strand breaks through the homologous recombination pathway. This deficiency can result from mutations in BRCA1, BRCA2, or other homologous recombination genes, or from epigenetic silencing. HRD creates a therapeutic vulnerability through synthetic lethality with PARP inhibition, as cells become dependent on alternative repair pathways. HRD testing combines genomic scarring signatures with mutation analysis to identify patients likely to benefit from PARP inhibitor therapy.
Usage
Usage note: HRD is broader than BRCA deficiency; avoid using terms interchangeably.
In Context
- "The patient's tumor showed homologous recombination deficiency, predicting olaparib sensitivity." — Precision oncology treatment plan
- "Homologous recombination deficiency extends beyond BRCA mutations to include multiple pathway genes." — Scientific review article