Homologous Recombination Deficiency Testing for BRCA-Like Tumors: The Road to Clinical Validation
Marjolijn M. Ladan, Dik C. van Gent, Agnes Jager
Abstract
Germline BRCA mutations result in homologous recombination deficiency (HRD) in hereditary breast and ovarian cancer, as well as several types of sporadic tumors. The HRD phenotype makes these tumors sensitive to DNA double strand break-inducing agents, including poly-(ADP-ribose)-polymerase (PARP) inhibitors. Interestingly, a subgroup of cancers without a BRCA mutation also shows an HRD phenotype. Various methods for selecting patients with HRD tumors beyond BRCA-mutations have been explored. These methods are mainly based on DNA sequencing or functional characteristics of the tumor. We here discuss the various tests and the status of their clinical validation.
Topics & Concepts
Homologous recombinationCancer researchPoly ADP ribose polymeraseGermlineOvarian cancerPolymeraseGermline mutationMutationPhenotypeHomologous chromosomeGenetic testingDNA repairDNAMedicineCancerGeneticsBiologyGenePARP inhibition in cancer therapyDNA Repair MechanismsBRCA gene mutations in cancer