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Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy
SIMPLE SUMMARY: The Italian population is characterized by a high genetic heterogeneity mostly due to its long history of migration and colonization and to its geographical conformation. Consistently, several BRCA1/2 pathogenic variants (PVs) have been reported to be recurrent or even founder in def...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866799/ https://www.ncbi.nlm.nih.gov/pubmed/33573335 http://dx.doi.org/10.3390/cancers13030532 |
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author | Figlioli, Gisella De Nicolo, Arcangela Catucci, Irene Manoukian, Siranoush Peissel, Bernard Azzollini, Jacopo Beltrami, Benedetta Bonanni, Bernardo Calvello, Mariarosaria Bondavalli, Davide Pasini, Barbara Vignolo Lutati, Francesca Ogliara, Paola Zuradelli, Monica Pensotti, Valeria De Vecchi, Giovanna Volorio, Sara Verderio, Paolo Pizzamiglio, Sara Matullo, Giuseppe Aneli, Serena Birolo, Giovanni Zanardi, Federica Tondini, Carlo Zambelli, Alberto Livraghi, Luca Franchi, Michela Radice, Paolo Peterlongo, Paolo |
author_facet | Figlioli, Gisella De Nicolo, Arcangela Catucci, Irene Manoukian, Siranoush Peissel, Bernard Azzollini, Jacopo Beltrami, Benedetta Bonanni, Bernardo Calvello, Mariarosaria Bondavalli, Davide Pasini, Barbara Vignolo Lutati, Francesca Ogliara, Paola Zuradelli, Monica Pensotti, Valeria De Vecchi, Giovanna Volorio, Sara Verderio, Paolo Pizzamiglio, Sara Matullo, Giuseppe Aneli, Serena Birolo, Giovanni Zanardi, Federica Tondini, Carlo Zambelli, Alberto Livraghi, Luca Franchi, Michela Radice, Paolo Peterlongo, Paolo |
author_sort | Figlioli, Gisella |
collection | PubMed |
description | SIMPLE SUMMARY: The Italian population is characterized by a high genetic heterogeneity mostly due to its long history of migration and colonization and to its geographical conformation. Consistently, several BRCA1/2 pathogenic variants (PVs) have been reported to be recurrent or even founder in defined geographical areas including the Bergamo province in Northern Italy. In this study, we retrospectively analyzed the data from 1019 women affected with breast cancer with BRCA1/2 PVs. We compared the BRCA1/2 PVs spectrum found in the carrier individuals from the Bergamo province (BGP) with that of the general Italian population. We found that the majority of the BGP PVs had a local origin and remained confined to the BGP or to the surrounding Lombardy region. We also observed that the BGP BRCA1/2 PV spectrum is private and conserved comprising a smaller number of variants with an average higher frequency with respect to that of carrier individuals from the rest of Italy. 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. |
format | Online Article Text |
id | pubmed-7866799 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78667992021-02-07 Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy Figlioli, Gisella De Nicolo, Arcangela Catucci, Irene Manoukian, Siranoush Peissel, Bernard Azzollini, Jacopo Beltrami, Benedetta Bonanni, Bernardo Calvello, Mariarosaria Bondavalli, Davide Pasini, Barbara Vignolo Lutati, Francesca Ogliara, Paola Zuradelli, Monica Pensotti, Valeria De Vecchi, Giovanna Volorio, Sara Verderio, Paolo Pizzamiglio, Sara Matullo, Giuseppe Aneli, Serena Birolo, Giovanni Zanardi, Federica Tondini, Carlo Zambelli, Alberto Livraghi, Luca Franchi, Michela Radice, Paolo Peterlongo, Paolo Cancers (Basel) Article SIMPLE SUMMARY: The Italian population is characterized by a high genetic heterogeneity mostly due to its long history of migration and colonization and to its geographical conformation. Consistently, several BRCA1/2 pathogenic variants (PVs) have been reported to be recurrent or even founder in defined geographical areas including the Bergamo province in Northern Italy. In this study, we retrospectively analyzed the data from 1019 women affected with breast cancer with BRCA1/2 PVs. We compared the BRCA1/2 PVs spectrum found in the carrier individuals from the Bergamo province (BGP) with that of the general Italian population. We found that the majority of the BGP PVs had a local origin and remained confined to the BGP or to the surrounding Lombardy region. We also observed that the BGP BRCA1/2 PV spectrum is private and conserved comprising a smaller number of variants with an average higher frequency with respect to that of carrier individuals from the rest of Italy. 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. MDPI 2021-01-30 /pmc/articles/PMC7866799/ /pubmed/33573335 http://dx.doi.org/10.3390/cancers13030532 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Figlioli, Gisella De Nicolo, Arcangela Catucci, Irene Manoukian, Siranoush Peissel, Bernard Azzollini, Jacopo Beltrami, Benedetta Bonanni, Bernardo Calvello, Mariarosaria Bondavalli, Davide Pasini, Barbara Vignolo Lutati, Francesca Ogliara, Paola Zuradelli, Monica Pensotti, Valeria De Vecchi, Giovanna Volorio, Sara Verderio, Paolo Pizzamiglio, Sara Matullo, Giuseppe Aneli, Serena Birolo, Giovanni Zanardi, Federica Tondini, Carlo Zambelli, Alberto Livraghi, Luca Franchi, Michela Radice, Paolo Peterlongo, Paolo Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy |
title | Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy |
title_full | Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy |
title_fullStr | Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy |
title_full_unstemmed | Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy |
title_short | Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy |
title_sort | analysis of italian brca1/2 pathogenic variants identifies a private spectrum in the population from the bergamo province in northern italy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866799/ https://www.ncbi.nlm.nih.gov/pubmed/33573335 http://dx.doi.org/10.3390/cancers13030532 |
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