title: Non-founder BRCA1 mutations in Russian breast cancer patients.
abstract: 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 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 G1706E 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, 3819del5, 3875del4) were considered with respect to their possible founder effect and tested in the additional series of 210 high-risk BC patients; two BRCA heterozygotes (2080delA and 3819del5) were revealed. We conclude that the non-founder mutations constitute the minority of BRCA1 defects in Russia.
authors: N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia.
authors: Aglaya G
authors: AG
authors: Iyevleva
authors: Evgeny N
authors: EN
authors: Suspitsin
authors: Karin
authors: K
authors: Kroeze
authors: Tatiana V
authors: TV
authors: Gorodnova
authors: Anna P
authors: AP
authors: Sokolenko
authors: Konstantin G
authors: KG
authors: Buslov
authors: Dmitry A
authors: DA
authors: Voskresenskiy
authors: Alexandr V
authors: AV
authors: Togo
authors: Sergey P
authors: SP
authors: Kovalenko
authors: Nienke van der
authors: Nv
authors: Stoep
authors: Peter
authors: P
authors: Devilee
authors: Evgeny N
authors: EN
authors: Imyanitov
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D018703:Founder Effect; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D021141:Nucleic Acid Amplification Techniques; D010051:Ovarian Neoplasms / Q000235:genetics; D012307:Risk Factors; D012426:Russia
chemical_list: D019313:BRCA1 Protein; D004273:DNA, Neoplasm