TY - JOUR
T1 - Prevalence of BRCA1 genomic rearrangements in a large cohort of Italian breast and breast/ovarian cancer families without detectable BRCA1 and BRCA2 point mutations
AU - Agata, Simona
AU - Viel, Alessandra
AU - Della Puppa, Lara
AU - Cortesi, Laura
AU - Fersini, Giusi
AU - Callegaro, Monia
AU - Dalla Palma, Maurizia
AU - Dolcetti, Riccardo
AU - Federico, Massimo
AU - Venuta, Salvatore
AU - Miolo, Gianmaria
AU - D'Andrea, Emma
AU - Montagna, Marco
PY - 2006/9
Y1 - 2006/9
N2 - 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.
AB - 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.
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U2 - 10.1002/gcc.20342
DO - 10.1002/gcc.20342
M3 - Article
C2 - 16715518
AN - SCOPUS:33746795547
VL - 45
SP - 791
EP - 797
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
SN - 1045-2257
IS - 9
ER -