title: A new mutation of BRCA2 gene in an Italian healthy woman with familial breast cancer history.
abstract: Heterozygous germ line mutations in the Breast CAncer1 (BRCA1) and BRCA2 genes can lead to a high risk of breast and ovarian cancer, in addition to a significantly increased susceptibility of pancreatic, prostate and male breast cancer. The BRCA2 belongs to the tumor suppressor gene family and the protein encoded by this gene is involved in the repair of chromosomal damage, with an important role in the error-free repair of DNA double strand breaks. After complete sequencing of coding regions and splice junctions of both genes, in a family with breast cancer history, a non previously reported heterozygous mutation in BRCA2 was detected and studied in an Italian healthy female. The direct sequencing disclosed, on exon 15, an insertion (7525_7526insT). The frame shift mutation of BRCA2 causes a disruption of the translational reading frame, resulting in a stop codon 29 amino acids downstream, in the 2538 position of the BRCA2 protein. The mutated allele codifies a truncated protein, lacking the two putative nuclear localization signals (NLSs) that reside within the extreme C-terminal domain of BRCA2. Since this mutant protein not performs a translocation into the nucleus, it is fully non-functional.
authors.affiliation: Molecular Biology and Experimental Oncology Lab, Oncological Hospital, Lecce, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pisanò
authors.forename: Valeria
authors.initials: V
authors.lastname: Mezzolla
authors.forename: Maria Maddalena
authors.initials: MM
authors.lastname: Galante
authors.forename: Giovanni
authors.initials: G
authors.lastname: Alemanno
authors.forename: Corrado
authors.initials: C
authors.lastname: Manca
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Antonio
authors.initials: A
authors.lastname: Malvasi
authors.forename: Andrea
authors.initials: A
authors.lastname: Tinelli
mesh_terms: D000328:Adult; D024682:BRCA2 Protein / Q000235:genetics*; D001483:Base Sequence; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control*; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D010375:Pedigree; D012307:Risk Factors; D012689:Sequence Homology, Nucleic Acid; D016387:Women's Health
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D019913:Nuclear Localization Signals