A few founder BRCA1 mutations (5382insC 4154delA 185delAG) account for up to 15% of high-risk (young-onset or familial or bilateral) breast cancer (BC) cases in Russia The impact of non founder... Show moreA few founder BRCA1 mutations (5382insC 4154delA 185delAG) account for up to 15% of high-risk (young-onset or familial or bilateral) breast cancer (BC) cases in Russia The impact of non founder BRCA1 mutations in this country is less studied in particular there are no reports analyzing gross rearrangements of this gene in the Russian patient series We selected for the study 95 founder mutation negative high-risk BC cases Combination of high-resolution melting (HRM) and sequencing revealed six presumably BC-associated alleles (2080delA, 4808C > G 5214C > T 5236G > A 5460G > T 5622C > T) and one variant of an unknown significance (4885G > A) The pathogenic role of the 5236G > A mutation leading to G1 706E substitution was further confirmed by the loss of heterozygosity analysis of the corresponding tumor tissue Multiplex ligation-dependent probe amplification (MLPA) revealed two additional BRCA1 heterozygotes which carried BRCA1 deletions involving exons 1-2 and 3-7 respectively Based on the results of this investigation and the review of prior Russian studies three BRCA1 mutations (2080delA 3819de15 3875del4) were considered with respect to their possible founder effect and tested in the additional series of 210 high-risk BC patients two BACA heterozygotes (2080delA and 3819de15) were revealed We conclude that the non-founder mutations constitute the minority of BRCA1 defects in Russia (C) 2010 Elsevier Ireland Ltd All rights reserved Show less
