Centrosome amplification as a possible mechanism for numerical chromosome aberrations in cerebral primitive neuroectodermal tumors with TP53 mutations

Although alterations in chromosome number have frequently been detected in human tumor cells and associated with tumor initiation and progression, the causal mechanisms are still not understood. One protein known to be involv ed in maintaining genetic stability is tumor suppressor p53. Tn mice, p53 h as been implicated in the maintenance of diploidy (Cross et al., 1995) and the regulation of centrosome duplication (Fukasawa et al., 1996). Here we r eport on cerebral primitive neuroectodermal tumors that lacked the wild-typ e p53 gene (TP53) and showed multiple numerical chromosome aberrations, as detected by comparative genomic hybridization. In these tumors, the centros ome number was significantly higher than in a control tumor without a detec ted TP53 mutation and with few chromosomal imbalances. These findings indic ate that abnormal centrosome amplification can occur in human tumors lackin g wild-type TP53 and may be a mechanism by which numerical chromosome aberr ations are generated.