[DNA structural features on the borders of ERBB2 amplicons in breast cancer]

In 25-30% of breast cancer tumor cases amplification of chromosome fragment around the ERBB2 underlies the increased expression of genes adjacent to ERBB2. Increased expression of genes within ERBB2-containing am- plicons may have an impact not only on the growth and development of the tumor, but on the sensitivity of the tumor to different types of anti-cancer therapies. The initial cause of amplification and the exact borders of ERBB2-amplified chromosome fragment are still not completely characterized. No specific DNA sequences were found on the junction regions at intrachromosomal DNA amplification. We hypothesized that amplification borders can be specified by DNA structural peculiarities rather than the particular DNA sequence. This study focused on the mapping of ERBB2 amplification borders in breast cancer and the search for unusual structural features of DNA at the borders of the identified amplicons. The copy number of 10 genes adjacent to ERBB2 were evaluated by real time PCR in 162 breast cancer samples. Several ERBB2-containing amplicons of various lengths were revealed. In the majority of the analyzed samples, the borders of these amplicons were located within ZNFNIA3 and RARA genes. A bioinformatics analysis of the nucleotide sequence peculiarities around ERBB2 gene revealed the presence of AT-rich DNA regions with high degree of flexibility. These regions were able to form stable secondary structures. Positions of these sites strongly coincide with the positions of the ERBB2-containing amplicon borders found in real time PCR experiments. On the base of results obtained one can suppose that the structural features of DNA are involved in the formation of ERBB2-containing amplicon borders in breast cancer cells and the data are of importance for understanding the mechanisms of oncogene amplification.