Phenotypic features and genetic characterization of male breast cancer families: identification of two recurrent BRCA2 mutations in north-east of Italy

Miolo, GianMaria, Della Puppa, Lara, Santarosa, Manuela, De Giacomi, Clelia, Veronesi, Andrea, Bidoli, Ettore, Tibiletti, Maria Grazia, Viel, Alessandra and Dolcetti, Riccardo (2006) Phenotypic features and genetic characterization of male breast cancer families: identification of two recurrent BRCA2 mutations in north-east of Italy. BMC Cancer, 6 . doi:10.1186/1471-2407-6-156


Author Miolo, GianMaria
Della Puppa, Lara
Santarosa, Manuela
De Giacomi, Clelia
Veronesi, Andrea
Bidoli, Ettore
Tibiletti, Maria Grazia
Viel, Alessandra
Dolcetti, Riccardo
Title Phenotypic features and genetic characterization of male breast cancer families: identification of two recurrent BRCA2 mutations in north-east of Italy
Journal name BMC Cancer   Check publisher's open access policy
ISSN 1471-2407
Publication date 2006-06-09
Sub-type Article (original research)
DOI 10.1186/1471-2407-6-156
Open Access Status DOI
Volume 6
Total pages 9
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background: Breast cancer in men is an infrequent occurrence, accounting for ∼1% of all breast tumors with an incidence of about 1:100,000. The relative rarity of male breast cancer (MBC) limits our understanding of the epidemiologic, genetic and clinical features of this tumor.

Methods: From 1997 to 2003, 10 MBC patients were referred to our Institute for genetic counselling and BRCA1/2 testing. Here we report on the genetic and phenotypic characterization of 10 families with MBC from the North East of Italy. In particular, we wished to assess the occurrence of specific cancer types in relatives of MBC probands in families with and without BRCA2 predisposing mutations. Moreover, families with recurrent BRCA2 mutations were also characterized by haplotype analysis using 5 BRCA2-linked dinucleotide repeat markers and 8 intragenic BRCA2 polymorphisms.

Results: Two pathogenic mutations in the BRCA2 gene were observed: the 9106C>T (Q2960X) and the IVS16-2A>G (splicing) mutations, each in 2 cases. A BRCA1 mutation of uncertain significance 4590C>G (P1491A) was also observed. In families with BRCA2 mutations, female breast cancer was more frequent in the first and second-degree relatives compared to the families with wild type BRCA1/2 (31.9% vs. 8.0% p = 0.001). Reconstruction of the chromosome phasing in three families and the analysis of three isolated cases with the IVS16-2A>G BRCA2 mutation identified the same haplotype associated with MBC, supporting the possibility that this founder mutation previously detected in Slovenian families is also present in the North East of our Country. Moreover, analysis of one family with the 9106C>T BRCA2 mutation allowed the identification of common haplotypes for both microsatellite and intragenic polymorphisms segregating with the mutation. Three isolated cases with the same mutation shared the same intragenic polymorphisms and three 5′ microsatellite markers, but showed a different haplotype for 3′ markers, which were common to all three cases.

Conclusion: The 9106C>T and the IVS16-2A>G mutations constitute recurrent BRCA2 mutations in MBC cases from the North-East of Italy and may be associated with a founder effect. Knowledge of these two recurrent BRCA2 mutations predisposing to MBC may facilitate the analyses aimed at the identification of mutation carriers in our geographic area.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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