TY - JOUR
T1 - A new mutation of BRCA2 gene in an Italian healthy woman with familial breast cancer history
AU - Pisanò, Maurizio
AU - Mezzolla, Valeria
AU - Galante, Maria Maddalena
AU - Alemanno, Giovanni
AU - Manca, Corrado
AU - Lorusso, Vito
AU - Malvasi, Antonio
AU - Tinelli, Andrea
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
KW - BRCA
KW - Breast cancer
KW - Familiar breast cancer
KW - Frame shift
KW - Genetic testing
KW - Germ line mutations
KW - Ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=79951847352&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951847352&partnerID=8YFLogxK
U2 - 10.1007/s10689-010-9389-7
DO - 10.1007/s10689-010-9389-7
M3 - Article
C2 - 20878484
VL - 10
SP - 65
EP - 71
JO - Familial Cancer
JF - Familial Cancer
SN - 1389-9600
IS - 1
ER -