Claudia Marchetti1, Angelo Minucci2, Marco D'Indinosante3, Raffaella Ergasti3, Martina Arcieri3, Ettore Domenico Capoluongo4, Antonella Pietragalla1, Chiara Caricato5, Giovanni Scambia6, Anna Fagotti3. 1. Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 2. Molecular and Genomic Diagnostics Laboratory, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 3. Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy. 4. Università Federico II-CEINGE, Biotecnologie Avanzate, Napoli, Italy. 5. Catholic University of the Sacred Heart, Rome, Italy. 6. Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy. Electronic address: giovanni.scambia@policlinicogemelli.it.
Abstract
OBJECTIVE: For many years, BRCA mutational status has only been considered as a predictor of ovarian cancer susceptibility and as a prognostic factor. Nonetheless, in the era of precision medicine, it has also become a predictive biomarker of response to platinum-based-chemotherapy and, more recently, to PARP-inhibitors, also in the frontline setting. We assessed the feasibility of a fresh frozen tissue-based-BRCA-screening workflow in a tertiary referral center. METHODS: We consecutively enrolled a series of 456 newly diagnosed FIGO-Stage IIIC-IV, high grade serous-ovarian cancer patients. All patients receiving tumor-biopsy underwent tBRCA-testing. RESULTS: Clinically relevant tissue-BRCA (tBRCA) variants were observed in 145 women (31.8%), particularly we recognized 89 (61.4%) patients with BRCA1-pathogenetic variants (PVs) and 56 women (38.6%) with BRCA2-PVs. Among 292 tBRCA wild-type (wt) patients, 88 cases were germline BRCA tested (gBRCA) and 86 (97.8%) were confirmed as gBRCAwt, while 1 (1.1%) had gBRCA variant of uncertain significance and 1 had gBRCA mutation (1.1%). The concordance of tumor test versus germline BRCA test was 86.3% (209/242). Large genomic rearrangements (LGRs) were suspected in 13/292 tBRCAwt patients (4.5%) by using bioinformatic algorithm and multiplex ligation-dependent probe amplification (MLPA) was performed, with evidence of PVs in only 1 case. CONCLUSIONS: Fresh-frozen tissue-based BRCA screening workflow is feasible and reliable. It allows to enlarge the BRCA mutated population that might receive PARPi with the greatest benefit, without missing cascade testing for family members and therefore, maintaining its preventive role.
OBJECTIVE: For many years, BRCA mutational status has only been considered as a predictor of ovarian cancer susceptibility and as a prognostic factor. Nonetheless, in the era of precision medicine, it has also become a predictive biomarker of response to platinum-based-chemotherapy and, more recently, to PARP-inhibitors, also in the frontline setting. We assessed the feasibility of a fresh frozen tissue-based-BRCA-screening workflow in a tertiary referral center. METHODS: We consecutively enrolled a series of 456 newly diagnosed FIGO-Stage IIIC-IV, high grade serous-ovarian cancerpatients. All patients receiving tumor-biopsy underwent tBRCA-testing. RESULTS: Clinically relevant tissue-BRCA (tBRCA) variants were observed in 145 women (31.8%), particularly we recognized 89 (61.4%) patients with BRCA1-pathogenetic variants (PVs) and 56 women (38.6%) with BRCA2-PVs. Among 292 tBRCA wild-type (wt) patients, 88 cases were germline BRCA tested (gBRCA) and 86 (97.8%) were confirmed as gBRCAwt, while 1 (1.1%) had gBRCA variant of uncertain significance and 1 had gBRCA mutation (1.1%). The concordance of tumor test versus germline BRCA test was 86.3% (209/242). Large genomic rearrangements (LGRs) were suspected in 13/292 tBRCAwt patients (4.5%) by using bioinformatic algorithm and multiplex ligation-dependent probe amplification (MLPA) was performed, with evidence of PVs in only 1 case. CONCLUSIONS: Fresh-frozen tissue-based BRCA screening workflow is feasible and reliable. It allows to enlarge the BRCA mutated population that might receive PARPi with the greatest benefit, without missing cascade testing for family members and therefore, maintaining its preventive role.
Authors: Margreet G E M Ausems; Joanne A de Hullu; Vera M Witjes; Jozé C C Braspenning; Nicoline Hoogerbrugge; Yvonne H C M Smolders; Dorien M A Hermkens; Marian J E Mourits; Marjolijn J L Ligtenberg Journal: Fam Cancer Date: 2022-05-16 Impact factor: 2.375
Authors: Angelo Minucci; Giovanni Scambia; Maria De Bonis; Elisa De Paolis; Concetta Santonocito; Anna Fagotti; Ettore Capoluongo; Paola Concolino; Andrea Urbani Journal: Mol Biol Rep Date: 2020-12-12 Impact factor: 2.316
Authors: Claudia Marchetti; Marco D'Indinosante; Carolina Bottoni; Chiara Di Ilio; Stefano Di Berardino; Barbara Costantini; Angelo Minucci; Laura Vertechy; Giovanni Scambia; Anna Fagotti Journal: Sci Rep Date: 2021-05-27 Impact factor: 4.379