RT Journal Article
SR Electronic
T1 Large genomic deletions inactivate the BRCA2 gene in breast cancer families
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP e64
OP e64
DO 10.1136/jmg.2005.032789
VO 42
IS 10
A1 S Agata
A1 M Dalla Palma
A1 M Callegaro
A1 M C Scaini
A1 C Menin
A1 C Ghiotto
A1 O Nicoletto
A1 G Zavagno
A1 L Chieco-Bianchi
A1 E D’Andrea
A1 M Montagna
YR 2005
UL http://jmg.bmj.com/content/42/10/e64.abstract
AB Background:BRCA1 and BRCA2 are the two major genes responsible for the breast and ovarian cancers that cluster in families with a genetically determined predisposition. However, regardless of the mutation detection method employed, the percentage of families without identifiable alterations of these genes exceeds 50%, even when applying stringent criteria for family selection. A small but significant increase in mutation detection rate has resulted from the discovery of large genomic alterations in BRCA1. A few studies have addressed the question of whether BRCA2 might be inactivated by the same kinds of alteration, but most were either done on a relatively small number of samples or employed cumbersome mutation detection methods of variable sensitivity. Objective: To analyse 121 highly selected families using the recently available BRCA2 multiplex ligation dependent probe amplification (MLPA) technique. Results: Three different large genomic deletions were identified and confirmed by analysis of the mutant transcript and genomic characterisation of the breakpoints. Conclusions: Contrary to initial suggestions, the presence of BRCA2 genomic rearrangements is worth investigating in high risk breast or ovarian cancer families.