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Clinical implications of germline and somatic genetic testing in ovarian carcinoma: BRCA and beyond. The PERSONA-Ovary trial.

I. Betella Emanuele Bonetti L. Ribero C. Zanzottera Caterina Fumagalli C. Sangalli A. Garbi Abbondanza Montinaro F. Multinu E. Marino G. Bonizzi Matteo Dal Molin Elena Belloni Maria Capra S. Kahler-Ribeiro-Fontana E. Rioldi Alessandra Saraca I. Feroce Ada Sbriglia D. Vacirca Isabella Sala Vincenzo Bagnardi G. Peruzzotti Nicola Fusco F. Peccatori V. Galimberti Elena Guerini Rocco B. Bonanni N. Colombo L. Mazzarella

Oct 2026 · Gynecologic Oncology · Vol 214, pp. 110-118 · 0 citations · 18 references

Medicine

Abstract

Objective

The PERSONA-Ovary study evaluated germline pathogenic/likely-pathogenic variant prevalence, feasibility of unselected multigene testing integration in routine clinical care, and germline-somatic BRCA concordance in ovarian cancer patients.

Methods

We conducted a prospective observational study of consecutive ovarian carcinoma patients treated at a tertiary-cancer care center, between July 2018 and September 2021. Germline multigene panel testing was performed using next-generation sequencing. Feasibility was assessed by informative rate and turnaround time. Germline-somatic concordance was assessed in patients with paired tumor BRCA results.

Results

Among 320 patients, pathogenic/likely-pathogenic variants were identified in 95 (29.7%, 95% CI 24.7-35.0); 81 (85.3%, 95% CI 76.5-91.7) carried mutations in ovarian cancer susceptibility genes, including 60 with BRCA alterations (63.2%, BRCA1 n=43, BRCA2 n=17). Germline testing was informative in all patients (100%). Median turnaround time was 221days (IQR 173-284), improving significantly across study periods (p<0.001). Tumor BRCA testing was available in 298 patients (93.1%), with germline-somatic concordance of 94.0% (κ=0.82, 95% CI 0.72-0.90). A germline-first strategy with reflex tumor testing achieved complete detection with fewer assays than parallel testing; a tumor-first strategy required the fewest assays (366 vs 596) but missed two germline BRCA carriers (detection rate of 96.3%).

Conclusion

Unselected germline multigene panel testing was technically feasible and clinically informative in routine ovarian cancer care. Pathogenic/likely-pathogenic variants were identified in 29.7% of patients, supporting germline testing integration into contemporary ovarian cancer management. Although germline-first strategies maximize hereditary cancer detection, dedicated molecular workflows remain necessary to ensure clinically actionable turnaround times.

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