Author(s): Ivanka Dimova, Radka Tafradzhiska-Hadzhiolova, Svilen Maslyankov, Desislava Nesheva, Draga Toncheva
Despite of the large number of molecular studies in breast cancer, the data are still insufficient for understanding its molecular pathogenesis. The dramatic development of genetics in recent years has made it possible to gain insight into the molecular mechanisms of tumorigenesis. The aims of the study was to determine the type, frequency and fine mapping of unbalanced genomic alterations in ductal carcinoma of the breast. For this study we have used tumor samples of invasive ductal breast cancer to be analysed by comparative genomic hybridization on DNA microarrays. Two approaches were applied in the analysis of significant unbalanced genomic changes: a) identification of clones which presented unbalanced changes (log2 T: H> +0.25 for gain and <-0.25 for losses) in more than 70% of the tumors; b) establishing clones which harbor amplifications (log2 T: H> +0.5) or homozygous deletions (log2 T: H <- 0.5) in more than 50% of tumors. Our results showed that the most commonly affected chromosome arms by gains were 20q and 1q. Loss at high frequency was found in 8p. Totally 9 regions with high rate of genetic alterations (7 in short and 2 in long arm) were detected in chromosome 1. Genetic losses in chromosome 8 predominated - 8p11.21 have lost in 100% of the cases. There were regions of chromosome 17 with a frequency of genetic gains over 70% - in 17q12, 17q21.31, 17q22 and a region with a frequency of more than 80% loss in 17q21.32. The long arm of chromosome 20 was affected by significant amplifications in 10 regions, but with the highest frequency of more than 80% in 20q11.21-q11.23, 20q12 and 20q13.12-q13.2. Our study contributed to the fine mapping of genomic imbalances in ductal breast cancer, suggesting the significant regions of genetic gains and losses. The genes in the found regions could represent potential oncogenes and/or tumor-supressor genes with cancer-emerging role.
ductal breast cancer, array CGH, oncogenes and tumor-supressor genes
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