Altered centrosome structure is associated with abnormal mitoses in human breast tumors

Centrosomes are the major microtubule organizing center in mammalian cells and establish the spindle poles during mitosis, Centrosome defects have bee n implicated in disease and tumor progression and have been associated with nullizygosity of the p53 tumor suppressor gene. In the present ultrastruct ural analysis of 31 human breast tumors, we found that centrosomes of most tumors had significant alterations compared to centrosomes of normal breast tissue. These alterations in included 1) supernumerary centrioles, 2) exce ss pericentriolar material, 3) disrupted centriole barrel structure, 4) uni ncorporated microtubule complexes, 5) centrioles of unusual length, 6) cent rioles functioning as ciliary basal bodies,;and 7) mispositioned centrosome s. These alterations are associated with changes in cell polarity, changes in cell and tissue differentiation, and chromosome missegregation through m ultipolar mitoses, Significantly, the presence of excess pericentriolar mat erial was associated with the highest frequency of abnormal mitoses. Centro some abnormalities may confer a mutator phenotype to tumors, occasionally y ielding cells with a selective advantage that emerge and thrive, thus leadi ng the tumor to a more aggressive state.