Objective
The project consists of 2 main parts. The first one is aimed to define the specific features of the pattern of allelic losses in multiple breast carcinomas (MBC). The second part will focus on the influence of populational differences on the links between HRAS-1 genotype and BC risk.
The study of MBC will include an analysis of deletions at chromosomes 1p, 1q, 3p, 6q, 7q, 11p, 11q, 13q, 16q, 17p, 17q and 18q in each tumour from the same patients. This investigation will address the question, whether concordance or discordance of somatic genetic lesions is observed. Parallel examination of the these mutations in regular, single breast carcinomas (SBC) will allow to compare the frequencies of losses of heterozygosity (LOH) in MBC vs. SBC. The data will clarify, if the components of BC mollar pathogenesis are somewhat predetermined by an individual risk factor, or increased BC predisposition can be realised into the tumour progression by very alternative mutational events. The key points of study management will include the transfer of PCR technologies for LOH detection from European to Russian partners, joint efforts in the collection of MBC cases, distribution of experimental responsibilities as well as the consulting role of Dutch and French teams. The research on the impact of populational and geographical factors will concern genetic mechanisms of BC susceptibility. In particular, HRAS-1 allele distribution will be analysed in BC patients and healthy donors of Russian, French and Dutch origin. This study will result in the determination of BC associated HRAS-1 genotypes, and in the estimation of the significance of regional variations for the allele frequencies of this gene. Special efforts will be done to increase the value of the data. First, inclusion of elderly tumour-free women, which seem to represent "low BC risk" cohort, is expected to emphasise the essential differences between BC prone and tolerant genotypes. Second, comparison of jects from various geographical areas will be done by the same research team; that will allow to exclude the role of technical deviations in the data bias. Third, interlaboratory re-examination of selected cases will be involved. Collection of DNA samples will be done by all participating teams, HRAS-1 analysis will be performed in Russia, and interlaboratory control of the data will be carried out in France. Investigation of somatic mutations in MBC and the proposed design for HRAS-1 studies possess significant level of novelty.
All described activities are aimed to improve an understanding of biology of breast cancer.
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Programme(s)
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Coordinator
34033 Montpellier
France
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