title: Prevalence of BRCA1 and BRCA2 genomic rearrangements in a cohort of consecutive Italian breast and/or ovarian cancer families.
abstract: Germline point mutations in BRCA1 and BRCA2 genes account for about 30% of the inherited breast and ovarian cancers. Germline genomic rearrangements have been found in both BRCA1 and BRCA2 genes, but the extent to which these alterations might contribute to increasing the actual mutation detection rate is still debated. Here we screened a cohort of 112 consecutive Italian families at moderate-to-high risk for breast and/or ovarian cancer for BRCA1 and BRCA2 point mutations and genomic rearrangements. Of the 83 point mutation negative probands, two (2.4%) showed BRCA1 rearrangements, accounting for 10.5% of the BRCA1 mutations. BRCA1 del18-19 has been previously described in another Italian family, while the molecular characterization of the BRCA1 del23-24 is given here for the first time. Conversely, we failed to identify any BRCA2 rearrangements even in the hereditary breast cancer families, where we detected an higher prevalence of BRCA2 compared to BRCA1 point mutations. Our results support the idea that search for BRCA1 rearrangements should be included in the genetic screening of even moderate risk breast/ovarian cancer families. In contrast, they suggest BRCA2 rearrangements might be very rare out of the high risk families including a male breast cancer.
authors.affiliation: Department of Experimental Medicine, University La Sapienza, Policlinico Umberto I, Viale Regina Elena, 324, Rome 00161, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Buffone
authors.forename: Carlo
authors.initials: C
authors.lastname: Capalbo
authors.forename: Enrico
authors.initials: E
authors.lastname: Ricevuto
authors.forename: Tina
authors.initials: T
authors.lastname: Sidoni
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
authors.forename: Mario
authors.initials: M
authors.lastname: Falchetti
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Silverio
authors.initials: S
authors.lastname: Tomao
authors.forename: Christian
authors.initials: C
authors.lastname: Rinaldi
authors.forename: Massimo
authors.initials: M
authors.lastname: Zani
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferraro
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
authors.forename: Isabella
authors.initials: I
authors.lastname: Screpanti
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
mesh_terms: D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005190:Family; D005260:Female; D015321:Gene Rearrangement; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004273:DNA, Neoplasm