Multiple-gene panel analysis in a case series of 255 women with hereditary breast and ovarian cancer

// Gianluca Tedaldi 1 , Michela Tebaldi 1 , Valentina Zampiga 1 , Rita Danesi 2 , Valentina Arcangeli 3 , Mila Ravegnani 2 , Ilaria Cangini 1 , Francesca Pirini 1 , Elisabetta Petracci 4 , Andrea Rocca 5 , Fabio Falcini 2 , Dino Amadori 5 and Daniele Calistri 1 1 Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 2 Romagna Cancer Registry, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 3 Department of Medical Oncology, Ospedale Infermi, Rimini, Italy 4 Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 5 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy Correspondence to: Daniele Calistri, email: daniele.calistri@irst.emr.it Keywords: hereditary breast and ovarian cancer, multiple-gene panel, next-generation sequencing, bilateral breast cancer, cancer predisposition Received: October 19, 2016      Accepted: March 14, 2017      Published: April 03, 2017 ABSTRACT As new genes predisposing to breast (BC) and ovarian cancer (OC) are constantly emerging, the use of panels of genes analyzed by Next-Generation Sequencing (NGS) is increasing in clinical diagnostics. The identification of a large number of new germline mutations allows for deeper knowledge of cancer predisposition, although raising many questions about patient management. BC and OC patients recruited by our counseling service between 2012-2015 were included in this study. DNA was extracted from peripheral blood and a panel of 94 genes involved in hereditary tumors was analyzed by NGS. Patient clinical features of BC and OC and cancer family history were collected and compared to the patient genetic profile. A total of 255 women were analyzed, 57 of whom had a pathogenic mutation in BRCA1/2 genes, and 17 carried pathogenic mutations in other genes, such as PALB2 , ATM , BRIP1 , RAD51D , MSH6 , PPM1D , RECQL4 , ERCC3 , TSC2 , SLX4 and other Fanconi anemia genes. Patients with a pathogenic mutation in genes other than BRCA1 and BRCA2 showed no significant difference from the BRCA1/2 -mutated carriers with respect to age at diagnosis and clinical features, suggesting that mutations in other genes could pose a high risk of cancer development. These patients had a much higher percentage of bilateral breast cancer (BBC) and a lower rate of OC than BRCA -mutated patients and patients with no pathogenic mutations: as a consequence, the surveillance protocol should be customized to the patient genetic characteristics.