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Erschienen in: Breast Cancer Research and Treatment 3/2014

01.12.2014 | Epidemiology

Novel and recurrent BRCA2 mutations in Italian breast/ovarian cancer families widen the ovarian cancer cluster region boundaries to exons 13 and 14

verfasst von: Anna Coppa, Amelia Buffone, Carlo Capalbo, Arianna Nicolussi, Sonia D’Inzeo, Francesca Belardinilli, Valeria Colicchia, Marialaura Petroni, Teresa Granato, Cecilia Midulla, Massimo Zani, Sergio Ferraro, Isabella Screpanti, Alberto Gulino, Giuseppe Giannini

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2014

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Abstract

Hereditary breast and ovarian cancer are mainly linked to mutations in BRCA1 and BRCA2 genes which confer a similar cumulative risk of developing breast cancer. Importantly, while BRCA2 mutation carriers generally have a lower cumulative risk for ovarian cancer, mutations clustered in the central portion of BRCA2 are associated with a higher proportion of ovarian compared with breast cancer cases. The boundaries of this ovarian cancer cluster region (OCCR) have been tentatively defined within a 3.3 kb region of BRCA2 exon 11, and herein, we reassessed these boundaries using our series of Italian breast/ovarian cancer families. We used direct sequencing to investigate BRCA mutations in 367 breast/ovarian cancer families. We also studied the association between the location of the mutations and the ovarian cancer phenotype in our cohort of BRCA2-mutated families. We observed the novel c.7309_7309delA frameshift mutation and the c.7007G>A deleterious mutation in BRCA2 exons 14 and 13, respectively, in five independent Italian families characterized by a high proportion of ovarian cancer cases. Of note, a significantly higher proportion of ovarian versus breast cancer cases was associated not only with mutations in the previously defined OCCR (OR = 5.91; p = 0.004), but also with the exon 13–14 region (OR = 7.37; p = 0.001) in our BRCA2-mutated families. Our data provide initial evidence for a novel putative OCCR in BRCA2 exons 13–14.
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Metadaten
Titel
Novel and recurrent BRCA2 mutations in Italian breast/ovarian cancer families widen the ovarian cancer cluster region boundaries to exons 13 and 14
verfasst von
Anna Coppa
Amelia Buffone
Carlo Capalbo
Arianna Nicolussi
Sonia D’Inzeo
Francesca Belardinilli
Valeria Colicchia
Marialaura Petroni
Teresa Granato
Cecilia Midulla
Massimo Zani
Sergio Ferraro
Isabella Screpanti
Alberto Gulino
Giuseppe Giannini
Publikationsdatum
01.12.2014
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 3/2014
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-014-3196-z

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