Detection of Her2/neu, c-MYC and ZNF217 gene amplification during breast cancer progression using fluorescence in situ hybridization.

The deletion of tumor suppressor genes and amplification of activating oncogenes appear to be critical events in tumorigenesis. We carried out fluorescence in situ hybridization (FISH) analysis of the breast cancer cell line MCF7 and clinically obtained cancer tissue sections on the basis of which we suggest a breast cancer development model. We selected 28 genes for FISH probes from breast cancer patients. Of the 28 genes studied, 14 were shown to be consistently amplified in the breast cancer cell line MCF7. We selected three genes from clinical tumor samples on the basis of results from MCF7 analysis. The amplification of Her2/neu or ZNF217 is closely associated with the stages of breast cancer. The frequency of amplification of Her2/neu increased notably in patients at stages later than IIB based on TNM staging, whereas the amplification of ZNF217 correlated with T2N1M0 at stage IIB and later stages. c-MYC amplification was not related to the stage. Her2/neu, ZNF217 and c-MYC were found to have a significantly increased copy number in breast cancer cells. In breast cancer progression, c-MYC amplification is an early event, while ZNF217 and Her2/neu amplification may play a role in the later stage of tumor development.