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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Tuesday, January 21, 2025
Isabelle Ray-Coquard, MD, PhD, of Centre Léon Bérard and University Claude Bernard Lyon, France, and colleagues combined genomic data from patients with high-grade ovarian cancer from six trials that evaluated the PARP inhibitor olaparib to shed light on the potential causes and patterns of genomic instability. Published in Genome Medicine, the results of this trial concluded that among patients with ovarian cancer, genomic instability is a positive predictor of PARP inhibitor response.
“This analysis [provides] valuable insight into patterns of genomic instability and potential drivers of homologous recombination deficiency (HRD), other than BRCA mutations, among patients with ovarian cancer,” the study authors concluded. “These data will help guide future research into the potential clinical effectiveness of anticancer treatments in ovarian cancer, including PARP inhibitors as well as other precision oncology agents.”
A total of 2,147 tumor samples were collected from trials SOLO1, PAOLA-1, Study 19, SOLO2, OPINION, and LIGHT. The PARP inhibitor olaparib was the treatment under focus across these studies. Each sample was evaluated for HRD using next-generation sequencing. BRCA1- and/or BRCA2-mutated, non-BRCA homologous recombination repair (HRR)-mutated, and non-HRR–mutated tumors were assessed for genomic instability.
BRCA-mutated tumors demonstrated significantly higher genomic instability scores compared with non-BRCA–mutated tumors (P < .001) and had a high rate of high biallelic loss (97.3%). Among non-BRCA HRR-mutated tumors, 45.5% were HRD; a similar proportion of tumors were not (43.0%). Of note, non-HRR–mutated and non-BRCA HRR-mutated tumors appeared to have highly variable genomic instability scores.
In addition, median genomic instability scores among non-BRCA HRR tumors were significantly higher compared with non-HRR–mutated tumors (P = .003). Genetic mutations in the HRR genes RAD51D, PALB2, RAD51C, and BRIP1 were associated with high genomic instability. This was also found to be true among non-HRR genes RB1 and NF1.
Disclosure: For full disclosures of the study authors, visit genomemedicine.biomedcentral.com.
