A new mutation of BRCA2 gene in an Italian healthy woman with familial breast cancer history.
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.
Pisanò
Maurizio
M
Molecular Biology and Experimental Oncology Lab, Oncological Hospital, Lecce, Italy.
Mezzolla
Valeria
V
Galante
Maria Maddalena
MM
Alemanno
Giovanni
G
Manca
Corrado
C
Lorusso
Vito
V
Malvasi
Antonio
A
Tinelli
Andrea
A
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
D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D019913:Nuclear Localization Signals