title: Prevalence of BRCA1 genomic rearrangements in a large cohort of Italian breast and breast/ovarian cancer families without detectable BRCA1 and BRCA2 point mutations.
abstract: The presence of genomic rearrangements of the BRCA1 gene in breast and/or ovarian cancer families has been intensively investigated in patients from various countries over the last years. A number of different rearrangements have been reported by several studies that clearly document the involvement of this mutation type in genetic predisposition to breast and ovarian cancer. Population-specific studies are now needed to evaluate the prevalence of genomic rearrangements before deciding whether to include ad hoc screening procedures into standard diagnostic mutation detection approaches. Indeed, the vast majority of the studies have been performed on small, highly selected, sample sets because of the limitations imposed by the laborious technical approaches. Moreover, prevalence figures are likely to differ across different countries according to the ethnic origin of each specific population. Here we analyze a large cohort of 653 Italian probands, negative for BRCA1 and BRCA2 point mutations, gathered from four National Institutions. We report the identification of BRCA1 genomic rearrangements in 12 independent families. Noteworthy, half of the probands carry mutations that recur in more than one Italian family. Considering the whole spectrum of Italian BRCA1 gene rearrangements identified thus far in consecutive patients, we estimate that alterations of this type account for 19% (95% CI: 0.11 < 0.19 < 0.28) of the BRCA1 mutation positive families. We conclude that the search for major genomic rearrangements is essential for an accurate and comprehensive BRCA1 mutation detection strategy in Italy.
authors.affiliation: Department of Oncology and Surgical Sciences, Oncology Section, University of Padua, Padua, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Agata
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viel
authors.forename: Lara
authors.initials: L
authors.lastname: Della Puppa
authors.forename: Laura
authors.initials: L
authors.lastname: Cortesi
authors.forename: Giusi
authors.initials: G
authors.lastname: Fersini
authors.forename: Monia
authors.initials: M
authors.lastname: Callegaro
authors.forename: Maurizia
authors.initials: M
authors.lastname: Dalla Palma
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dolcetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.forename: Salvatore
authors.initials: S
authors.lastname: Venuta
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Miolo
authors.forename: Emma
authors.initials: E
authors.lastname: D'Andrea
authors.forename: Marco
authors.initials: M
authors.lastname: Montagna
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D015894:Genome, Human; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D017354:Point Mutation; D015995:Prevalence