39MO Clinical evaluation of a low-coverage whole-genome test for homologous recombination deficiency detection in ovarian cancer

Boidot, R.; Blum, M.G.B.; Wissler, M-P.; Gottin, C.; Ruzicka, J.; Duforet-Frebourg, N.; Jeanniard, A.; Just, P.-A.; Harter, P.; Pignata, S.; Martin, Andrew; Marth, C.; Mäenpää, J.; Colombo, N.; Vergote, I.B.; Fujiwara, K.; Bertrand, D.; Philippe, N.; Ray-Coquard, I.L.; Pujade-Lauraine, E.

doi:10.1016/j.esmoop.2023.100819

Cited by 2 publications

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“…As a testimony to the test’s ease of implementation, we observe an increase in the number of patients for which HRD status could be established relative to the alternative method. In addition, when the present results are compared to the results of recently developed alternative HRD detection solutions validated using a subset of the original PAOLA-1, we found that GIInger displays a higher accuracy, a lower rejection rate than the alternative tests, or both 39 , 40 , 41 , 42 , 43 , 44 ( Table S4 ).…”

Section: Discussionmentioning

confidence: 68%

GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles

Pozzorini,

Andre,

Coletta

et al. 2023

Cell Reports Medicine

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Section: Discussionmentioning

confidence: 68%

GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles

Pozzorini,

Andre,

Coletta

et al. 2023

Cell Reports Medicine

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“…sWGS HRD is based on the number of large-scale genomic alteration (LGA) which is defined as intra-chromosome arm CNA breaks with adjacent segments ≥ 10 Mb. While this specific algorithm has not yet been approved for clinical use in ovarian cancer, HRD signatures on sWGS by different academic (SWGS v2) and commercial (SeqOne HRD score) algorithms are undergoing validation in clinical samples from patients in phase III trials of PARPi (PALOA-1) [ 19 , 20 ]. Our results support that genomic instability testing is feasible on cftDNA from peritoneal fluid.…”

Section: Discussionmentioning

confidence: 99%

Homologous recombination deficiency (HRD) testing on cell-free tumor DNA from peritoneal fluid

Roussel-Simonin,

Blanc-Durand,

Tang

et al. 2023

Mol Cancer

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Background Knowing the homologous recombination deficiency (HRD) status in advanced epithelial ovarian cancer (EOC) is vital for patient management. HRD is determined by BRCA1/BRCA2 pathogenic variants or genomic instability. However, tumor DNA analysis is inconclusive in 15–19% of cases. Peritoneal fluid, available in > 95% of advanced EOC cases, could serve as an alternative source of cell-free tumor DNA (cftDNA) for HRD testing. Limited data show the feasibility of cancer panel gene testing on ascites cfDNA but no study, to date, has investigated HRD testing. Methods We collected ascites/peritoneal washings from 53 EOC patients (19 from retrospective cohort and 34 from prospective cohort) and performed a Cancer Gene Panel (CGP) using NGS for TP53/HR genes and shallow Whole Genome Sequencing (sWGS) for genomic instability on cfDNA. Results cfDNA was detectable in 49 out of 53 patients (92.5%), including those with limited peritoneal fluid. Median cfDNA was 3700 ng/ml, with a turnaround time of 21 days. TP53 pathogenic variants were detected in 86% (42/49) of patients, all with HGSOC. BRCA1 and BRCA2 pathogenic variants were found in 14% (7/49) and 10% (5/49) of cases, respectively. Peritoneal cftDNA showed high sensitivity (97%), specificity (83%), and concordance (95%) with tumor-based TP53 variant detection. NGS CGP on cftDNA identified BRCA2 pathogenic variants in one case where tumor-based testing failed. sWGS on cftDNA provided informative results even when tumor-based genomic instability testing failed. Conclusion Profiling cftDNA from peritoneal fluid is feasible, providing a significant amount of tumor DNA. This fast and reliable approach enables HRD testing, including BRCA1/2 mutations and genomic instability assessment. HRD testing on cfDNA from peritoneal fluid should be offered to all primary laparoscopy patients.

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39MO Clinical evaluation of a low-coverage whole-genome test for homologous recombination deficiency detection in ovarian cancer

Cited by 2 publications

References 0 publications

GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles

GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles

Homologous recombination deficiency (HRD) testing on cell-free tumor DNA from peritoneal fluid

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