Mutation screening of the BRCA1 and BRCA2 genes in probands with familial breast/ovarian cancer has beengreatly improved by the multiplex ligation-dependent probe amplification (MLPA) assay able to evidence generearrangements not detectable by standard screening methods. However, no criteria for selection of cases tobe submitted to the MLPA test have been reported yet. We used the BRCAPro software for the selection offamilial breast/ovarian cancer probands investigated with the MLPA approach after negative BRCA1/2conventional mutation screening. One hundred and seventy-seven probands were investigated for germlineBRCA1/2 mutations after assessment of genetic risk using BRCAPro. Probands were classified as BRCAPropositive (n = 67) when the carrier probability (CP) was >10% and as BRCAPro negative (n = 110), when the CPwas <10%. Conventional mutational analyses of the BRCA1/2 genes and, in one case, of p53 identified 22pathogenetic germline mutations, 12 in BRCA1, 9 in BRCA2 and 1 in p53, in 22/177 (12.4%) probands. All themutations except one were detected in BRCAPro-positive patients. In the 46 BRCAPro-positive cases thatresulted negative by BRCA1/2 mutation, screening analysis of rearrangements within BRCA1/2 by MLPA wascarried out. Three patients with a very high CP showed BRCA1 deletions, consisting of deletions of exons 1–2 intwo probands and of exon 24 in the third proband. In one case, the exons 1–2 deletion was shown tocosegregate with disease in the family. No BRCA2 rearrangements were detected, but one patient showed the1100delC of the CHEK2 gene, whose probe is present in the BRCA2 kit. In our series, the highest carrierdetection rate of mutation screening plus MLPA analysis (52.3%) was in patients with a BRCAPro CP >50%.
|Numero di pagine||7|
|Rivista||Annals of Oncology|
|Stato di pubblicazione||Published - 2007|
All Science Journal Classification (ASJC) codes