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.

Novel and recurrent BRCA2 mutations in Italian breast/ovarian cancer families widen the ovarian cancer cluster region boundaries to exons 13 and 14 / Coppa, Anna; Buffone, Amelia; Capalbo, Carlo; Nicolussi, Arianna; D'Inzeo, Sonia; Belardinilli, Francesca; Colicchia, Valeria; Petroni, Marialaura; Granato, T; Midulla, Cecilia; Zani, Massimo; Ferraro, Sergio; Screpanti, Isabella; Gulino, Alberto; Giannini, Giuseppe. - In: BREAST CANCER RESEARCH AND TREATMENT. - ISSN 0167-6806. - ELETTRONICO. - 148(3):3(2014), pp. 629-635. [10.1007/s10549-014-3196-z]

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

COPPA, Anna;BUFFONE, AMELIA;CAPALBO, CARLO;NICOLUSSI, Arianna;D'INZEO, SONIA;BELARDINILLI, FRANCESCA;COLICCHIA, VALERIA;PETRONI, MARIALAURA;MIDULLA, Cecilia;ZANI, Massimo;FERRARO, Sergio;SCREPANTI, Isabella;GULINO, Alberto;GIANNINI, Giuseppe
2014

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.
2014
01 Pubblicazione su rivista::01a Articolo in rivista
Novel and recurrent BRCA2 mutations in Italian breast/ovarian cancer families widen the ovarian cancer cluster region boundaries to exons 13 and 14 / Coppa, Anna; Buffone, Amelia; Capalbo, Carlo; Nicolussi, Arianna; D'Inzeo, Sonia; Belardinilli, Francesca; Colicchia, Valeria; Petroni, Marialaura; Granato, T; Midulla, Cecilia; Zani, Massimo; Ferraro, Sergio; Screpanti, Isabella; Gulino, Alberto; Giannini, Giuseppe. - In: BREAST CANCER RESEARCH AND TREATMENT. - ISSN 0167-6806. - ELETTRONICO. - 148(3):3(2014), pp. 629-635. [10.1007/s10549-014-3196-z]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/643801
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