The contribution of epigenetic changes to abnormal centrosomes and genomic instability in breast cancer.

The centrosome is the major microtubule organizing center of the cell and as such it plays an important role in cytoskeletal organization and in the formation of the bipolar mitotic spindle. Centrosome defects, characterized by abnormal size, number, and microtubule nucleation capacity, are distinguishing features of most high grade breast tumors and have been implicated as a possible cause for the loss of tissue architecture and the origin of mitotic abnormalities seen in solid tumors in general. Centrosome defects arise through uncoupling of centriole duplication and the cell cycle as a result of either genetic alterations or through physical or chemical perturbation of centrosome function. Centrosomes manifest unique epigenetic properties whereby positional or structural information can be propagated through somatic cell lineages by way of nongenetic pathways. Because aberrant centrosome function can result in chromosomal instability, these properties may have important implications for the origin of malignant breast tumors.