Two molecular cytogenetic views of breast cancer

Excerpt

This talk will present two views of genome evolution in human breast cancers using fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). FISH with chromosome-specific probes applied to thick tissue sections from tumors at several stages of progression reveals a remarkable level of cell-to-cell variability beginning with hyperplasia and increasing with increasing grade. These studies also demonstrate significant genomic evolution, including formation of polyploid nuclei within a single sample, suggesting a very high rate of genomic instability. These phenomena also were observed in vitro in few-cell clones established from breast cancer cell lines. Paradoxically, CGH analyses of 'average' genome copy number changes show relatively slow overall rates of evolution in vitro and in vivo. CGH karyotypes for breast cancer cell lines change relatively slowly as long as the environment remains constant. Likewise, CGH karyotypes of pairs of primary vs. metastatic or in situ vs. invasive breast tumors from the same patient are usually quite similar, suggesting a relatively slow rate of evolution. Possible explanations for this paradox will be discussed. …