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Genomic Instability: The Pivotal Role of Mutant P53 in Human Cancers

Silvia Di Agostino and Giovanni Blandino

The tumor suppressor p53 plays a critical role to preserve DNA fidelity from diverse insults through the regulation of cell-cycle checkpoints, DNA repair, senescence and apoptosis. The TP53 is altered in more than half of human cancers. This leads to the production of mutant p53 proteins that loose wild type p53 tumor suppression functions and concomitantly acquire new oncogenic deleterious features implicated in: increased cell proliferation, increased chemoresistance, disruption of tissue architecture, promotion of migration, invasion and metastasis and several other pro-oncogenic properties. Accumulating evidences suggest that mutant p53 proteins drastically perturb the residual genome-stabilizing mechanisms during cancer progression, thereby increasing genomic instability of mutant p53 carrying human cancers. In this commentary we briefly summarize the most important evidences suggesting that mutant p53 plays a relevant role in promoting genomic instability in human cancers.