Despite significant therapeutic advances, metastatic CRPC (mCRPC) remains a lethal disease. Mutations in homologous recombination repair (HRR) genes are frequent in mCRPC, and tumors harboring these mutations are known to be sensitive to PARP inhibitors. The aim of this study was to verify the technical effectiveness of this panel in the analysis of mCRPC, the frequency and type of mutations in the BRCA1/BRCA2 genes, as well as in the homologous recombination repair (HRR) genes. A total of 50 mCRPC cases were analyzed using a multi-gene next-generation sequencing panel evaluating a total of 1360 amplicons in 24 HRR genes. Of the 50 cases, 23 specimens (46.0%) had an mCRPC harboring a pathogenic variant or a variant of uncertain significance (VUS), whereas in 27 mCRPCs (54.0%), no mutations were detected (wild-type tumors). BRCA2 was the most commonly mutated gene (14.0% of samples), followed by ATM (12.0%), and BRCA1 (6.0%). In conclusion, we have set up an NGS multi-gene panel that is capable of analyzing BRCA1/BRCA2 and HRR alterations in mCRPC. Moreover, our clinical algorithm is currently being used in clinical practice for the management of patients with mCRPC.
International journal of molecular sciences. 2023 May 18*** epublish ***
Thais Maloberti, Antonio De Leo, Sara Coluccelli, Viviana Sanza, Elisa Gruppioni, Annalisa Altimari, Stefano Zagnoni, Francesca Giunchi, Francesco Vasuri, Michelangelo Fiorentino, Veronica Mollica, Simona Ferrari, Sara Miccoli, Michela Visani, Daniela Turchetti, Francesco Massari, Giovanni Tallini, Dario de Biase
Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy., Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy., Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy., Unit of Medical Genetics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy., Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy.