| Autor: |
Mazzuccato G; Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy., De Bonis M; Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy., Carboni V; Division of Oncological Gynecology, Department of Women's and Children's Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy., Marchetti C; Division of Oncological Gynecology, Department of Women's and Children's Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Catholic University of the Sacred Heart, Rome, Italy., Urbani A; Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. andrea.urbani@policlinicogemelli.it.; Catholic University of the Sacred Heart, Rome, Italy. andrea.urbani@policlinicogemelli.it., Scambia G; Division of Oncological Gynecology, Department of Women's and Children's Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Catholic University of the Sacred Heart, Rome, Italy., Capoluongo E; Università Federico II-CEINGE, Biotecnologie Avanzate, Naples, Italy., Fagotti A; Division of Oncological Gynecology, Department of Women's and Children's Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Catholic University of the Sacred Heart, Rome, Italy., Minucci A; Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. angelo.minucci@policlinicogemelli.it. |
| Abstrakt: |
Resistance can be the result of secondary tissue variants (STVs), which restore the open reading frame of the germline BRCA allele, producing functional BRCA protein in germline BRCA1/2 (BRCA) pathogenic variant (PV) carriers, treated with platinum-based chemotherapy or poly-(ADP-ribose) polymerase inhibitors (PARP-1). We reported recently a BRCA2 mutant high grade serous ovarian cancer (HGSOC) patient with acquired resistance to the PARP-1 olaparib due to a STV detected by next generation tumor sequencing (NGTS). The aim of this study was to evaluate the versatility of the high-resolution melting analysis (HRMA) obtained by magnetic induction cycler (MIC) to monitor the BRCA2 status in formalin-fixed paraffin-embedded (FFPE) tissue samples of this patient and to compare the results obtained by NGTS. HRMA highlighted the BRCA2 STV previously detected in the IIIrd HGSOC recurrence following the tissue BRCA2 tissue status comparing the high resolution melting profiles (HRMPs). HRMPs differentiate not only BRCA2 alleles, but also their different allele abundance. We underline that (1) the MIC uses a latest generation technology guaranteeing temperature uniformity and maintenance in each well allowing high and accurate performance to obtain reported results and (2) the HRMA maintains a high sensitivity and specificity when it is performed on FFPE samples. Finally, this study represents an additional use of the HRMA, confirming its extreme versatility in the diagnostic environment. |
Full text from SpringerLink