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Department of Pathology and Harvard Center for Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115 [S. D., K. M.], and Department of Pathology, Solid Tumor Cytogenetics [A. D.] and Division of Women’s and Perinatal Pathology, Department of Pathology [C. P. C.], Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
Genomic instability is a hallmark of malignant growth that frequently involves mitotic defects associated with centrosome abnormalities. However, the question of whether abnormal centrosomes cause genomic instability or develop secondary to other changes has not been conclusively resolved. Here we show that human papillomavirus (HPV)-16 E7 can induce abnormal centrosome synthesis before the development of extensive nuclear abnormalities. In contrast, expression of HPV-16 E6 is associated with marked nuclear atypia and concomitant accumulation of centrosomes. Our results demonstrate that HPV-16 E7-induced centrosome abnormalities represent an early event during neoplastic progression potentially driving genomic destabilization.
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