Cancers (Jan 2021)
Analysis of Italian <i>BRCA1/2</i> Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy
- Gisella Figlioli,
- Arcangela De Nicolo,
- Irene Catucci,
- Siranoush Manoukian,
- Bernard Peissel,
- Jacopo Azzollini,
- Benedetta Beltrami,
- Bernardo Bonanni,
- Mariarosaria Calvello,
- Davide Bondavalli,
- Barbara Pasini,
- Francesca Vignolo Lutati,
- Paola Ogliara,
- Monica Zuradelli,
- Valeria Pensotti,
- Giovanna De Vecchi,
- Sara Volorio,
- Paolo Verderio,
- Sara Pizzamiglio,
- Giuseppe Matullo,
- Serena Aneli,
- Giovanni Birolo,
- Federica Zanardi,
- Carlo Tondini,
- Alberto Zambelli,
- Luca Livraghi,
- Michela Franchi,
- Paolo Radice,
- Paolo Peterlongo
Affiliations
- Gisella Figlioli
- Genome Diagnostics Program, IFOM, FIRC Institute for Molecular Oncology, 20139 Milan, Italy
- Arcangela De Nicolo
- Cancer Genomics Program, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy
- Irene Catucci
- Genome Diagnostics Program, IFOM, FIRC Institute for Molecular Oncology, 20139 Milan, Italy
- Siranoush Manoukian
- Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Bernard Peissel
- Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Jacopo Azzollini
- Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Benedetta Beltrami
- Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Bernardo Bonanni
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
- Mariarosaria Calvello
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
- Davide Bondavalli
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
- Barbara Pasini
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
- Francesca Vignolo Lutati
- Medical Genetics Unit, University Hospital Città della Salute e della Scienza di Torino, 10126 Turin, Italy
- Paola Ogliara
- Medical Genetics Unit, University Hospital Città della Salute e della Scienza di Torino, 10126 Turin, Italy
- Monica Zuradelli
- Department of Oncology, IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy
- Valeria Pensotti
- Cancer Genetic Test Laboratory, Cogentech srl Società Benefit a Socio Unico, 20139 Milan, Italy
- Giovanna De Vecchi
- Cancer Genetic Test Laboratory, Cogentech srl Società Benefit a Socio Unico, 20139 Milan, Italy
- Sara Volorio
- Cancer Genetic Test Laboratory, Cogentech srl Società Benefit a Socio Unico, 20139 Milan, Italy
- Paolo Verderio
- Unit of Bioinformatics and Biostatistics, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Sara Pizzamiglio
- Unit of Bioinformatics and Biostatistics, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Giuseppe Matullo
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
- Serena Aneli
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
- Giovanni Birolo
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
- Federica Zanardi
- Bioinformatics Core Unit, IFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy
- Carlo Tondini
- Medical Oncology Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Alberto Zambelli
- Medical Oncology Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Luca Livraghi
- Medical Oncology Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Michela Franchi
- Medical Oncology Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Paolo Radice
- Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Paolo Peterlongo
- Genome Diagnostics Program, IFOM, FIRC Institute for Molecular Oncology, 20139 Milan, Italy
- DOI
- https://doi.org/10.3390/cancers13030532
- Journal volume & issue
-
Vol. 13,
no. 3
p. 532
Abstract
Germline pathogenic variants (PVs) in the BRCA1 or BRCA2 genes cause high breast cancer risk. Recurrent or founder PVs have been described worldwide including some in the Bergamo province in Northern Italy. The aim of this study was to compare the BRCA1/2 PV spectra of the Bergamo and of the general Italian populations. We retrospectively identified at five Italian centers 1019 BRCA1/2 PVs carrier individuals affected with breast cancer and representative of the heterogeneous national population. Each individual was assigned to the Bergamo or non-Bergamo cohort based on self-reported birthplace. Our data indicate that the Bergamo BRCA1/2 PV spectrum shows less heterogeneity with fewer different variants and an average higher frequency compared to that of the rest of Italy. Consistently, four PVs explained about 60% of all carriers. The majority of the Bergamo PVs originated locally with only two PVs clearly imported. The Bergamo BRCA1/2 PV spectrum appears to be private. Hence, the Bergamo population would be ideal to study the disease risk associated with local PVs in breast cancer and other disease-causing genes. Finally, our data suggest that the Bergamo population is a genetic isolate and further analyses are warranted to prove this notion.
Keywords