Irene Catucci1, Paolo Peterlongo1, Sara Ciceri1, Mara Colombo2, Graziella Pasquini2, Monica Barile3, Bernardo Bonanni3, Paolo Verderio4, Sara Pizzamiglio4, Claudia Foglia2, Anna Falanga5, Marina Marchetti5, Laura Galastri6, Tiziana Bianchi6, Chiara Corna7, Fernando Ravagnani8, Loris Bernard9, Stefano Fortuzzi10, Domenico Sardella10, Giulietta Scuvera11, Bernard Peissel11, Siranoush Manoukian11, Carlo Tondini7, Paolo Radice2. 1. 1] IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy [2] Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 2. Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 3. Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy. 4. Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 5. Department of Immunohematology and Transfusion Medicine, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. 6. Associazione Italiana Volontari Sangue Comunale Milano, Milan, Italy. 7. Unit of Medical Oncology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. 8. Immunohematology and Transfusion Medicine Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 9. Department of Experimental Oncology, Istituto Europeo di Oncologia, Cogentech, Milan, Italy. 10. IFOM Cogentech, Consortium for Genomic Technologies, Milan, Italy. 11. Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract
PURPOSE: Monoallelic germ-line deleterious mutations of PALB2 (partner and localizer of BRCA2) are associated with breast cancer risk and have been found in several populations, with carrier frequencies of ~1-2%. Initially, these mutations were considered to have moderate penetrance, but accumulating evidence now indicates that they are associated with much higher risk. METHODS: In this study, we sequenced the PALB2 coding regions unlinked to BRCA (breast cancer) genes in 575 probands from Italian breast cancer families recruited in Milan. RESULTS: We found 12 carriers (2.1%) of deleterious mutations, and none of the mutations was found in 784 controls collected in Milan. One of these mutations, the c.1027C>T (p.Gln343X), was found to be recurrent in the province of Bergamo in northern Italy, being detected in 6/113 (5.3%) familial breast cancer cases and 2/477 (0.4%) controls recruited in this area (Fisher's exact test: P < 0.01). CONCLUSIONS: Our data provide confirmatory findings that, in the Italian population also, deleterious mutations of PALB2 are relatively frequent predisposing factors for breast cancer and may be associated with high risk of the disease.
PURPOSE: Monoallelic germ-line deleterious mutations of PALB2 (partner and localizer of BRCA2) are associated with breast cancer risk and have been found in several populations, with carrier frequencies of ~1-2%. Initially, these mutations were considered to have moderate penetrance, but accumulating evidence now indicates that they are associated with much higher risk. METHODS: In this study, we sequenced the PALB2 coding regions unlinked to BRCA (breast cancer) genes in 575 probands from Italian breast cancer families recruited in Milan. RESULTS: We found 12 carriers (2.1%) of deleterious mutations, and none of the mutations was found in 784 controls collected in Milan. One of these mutations, the c.1027C>T (p.Gln343X), was found to be recurrent in the province of Bergamo in northern Italy, being detected in 6/113 (5.3%) familial breast cancer cases and 2/477 (0.4%) controls recruited in this area (Fisher's exact test: P < 0.01). CONCLUSIONS: Our data provide confirmatory findings that, in the Italian population also, deleterious mutations of PALB2 are relatively frequent predisposing factors for breast cancer and may be associated with high risk of the disease.
Authors: Irene Catucci; Silvia Casadei; Yuan Chun Ding; Sara Volorio; Filomena Ficarazzi; Anna Falanga; Marina Marchetti; Carlo Tondini; Michela Franchi; Aaron Adamson; Jessica Mandell; Tom Walsh; Olufunmilayo I Olopade; Siranoush Manoukian; Paolo Radice; Charite Ricker; Jeffrey Weitzel; Mary-Claire King; Paolo Peterlongo; Susan L Neuhausen Journal: Breast Cancer Res Treat Date: 2016-09-13 Impact factor: 4.872
Authors: Ciyu Yang; Ozge Ceyhan-Birsoy; Diana Mandelker; Sowmya Jairam; Amanda Catchings; Eileen M O'Reilly; Michael F Walsh; Liying Zhang Journal: Breast Cancer Res Treat Date: 2018-09-25 Impact factor: 4.872
Authors: Ella R Thompson; Kylie L Gorringe; Simone M Rowley; Michelle W Wong-Brown; Simone McInerny; Na Li; Alison H Trainer; Lisa Devereux; Maria A Doyle; Jason Li; Richard Lupat; Martin B Delatycki; Gillian Mitchell; Paul A James; Rodney J Scott; Ian G Campbell Journal: Breast Cancer Res Date: 2015-08-19 Impact factor: 6.466
Authors: Irene Catucci; Paolo Radice; Roger L Milne; Fergus J Couch; Melissa C Southey; Paolo Peterlongo Journal: Breast Cancer Res Date: 2016-11-09 Impact factor: 6.466