BRCA1 and BRCA2 point mutations and large rearrangements in breast and ovarian cancer families in Northern Poland

Sixty-four Polish families with a history of breast and/or ovarian cancer, fulfilling guidelines for genetic counselling, were screened for mutations in the BRCA1/2 genes using a combination of denaturing high performance liquid chromatography (DHPLC) and sequencing. Two thirds (43/64, 67%) of the families were found to carry deleterious mutations, of which the most frequent were BRCA1 5382insC (n=22/43; 51%) and Cys61Gly (n=9/43; 20%). Two other recurrent mutations were BRCA1 185delAG (n=3) and 3819del5 (n=4), together accounting for 16% of the 43 mutation positive cases. Other alterations found in this series of families included three novel mutations (BRCA1 2991del5, BRCA2 6238ins2del21 and 8876delC), which combined with findings from our earlier study of 60 Northern Polish families sum up to over a dozen distinct BRCA gene mutations discovered in this population. Moreover, screening of 43 BRCA1/2 negative families from the combined material for the presence of large rearrangements by multiplex ligation-dependent probe amplification (MLPA), resulted in the finding of two additional BRCA1 mutations: a deletion of exons 1A, 1B and 2 and a deletion of exons 17-19, both present