title: PALB2 sequencing in Italian familial breast cancer cases reveals a high-risk mutation recurrent in the province of Bergamo.
abstract: OBJECTIVE
  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.affiliation: 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.
authors.forename: Irene
authors.initials: I
authors.lastname: Catucci
authors.affiliation: 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.
authors.forename: Paolo
authors.initials: P
authors.lastname: Peterlongo
authors.affiliation: 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.
authors.forename: Sara
authors.initials: S
authors.lastname: Ciceri
authors.affiliation: Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Pasquini
authors.affiliation: Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Barile
authors.affiliation: Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Bonanni
authors.affiliation: Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Verderio
authors.affiliation: Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pizzamiglio
authors.affiliation: Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Foglia
authors.affiliation: Department of Immunohematology and Transfusion Medicine, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Falanga
authors.affiliation: Department of Immunohematology and Transfusion Medicine, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Marchetti
authors.affiliation: Associazione Italiana Volontari Sangue Comunale Milano, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Galastri
authors.affiliation: Associazione Italiana Volontari Sangue Comunale Milano, Milan, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bianchi
authors.affiliation: Unit of Medical Oncology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Corna
authors.affiliation: Immunohematology and Transfusion Medicine Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ravagnani
authors.affiliation: Department of Experimental Oncology, Istituto Europeo di Oncologia, Cogentech, Milan, Italy.
authors.forename: Loris
authors.initials: L
authors.lastname: Bernard
authors.affiliation: IFOM Cogentech, Consortium for Genomic Technologies, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fortuzzi
authors.affiliation: IFOM Cogentech, Consortium for Genomic Technologies, Milan, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Sardella
authors.affiliation: Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Giulietta
authors.initials: G
authors.lastname: Scuvera
authors.affiliation: Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Bernard
authors.initials: B
authors.lastname: Peissel
authors.affiliation: Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Siranoush
authors.initials: S
authors.lastname: Manoukian
authors.affiliation: Unit of Medical Oncology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Tondini
authors.affiliation: Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins