Mutational hotspots in the TP53 gene and, possibly, other tumor suppressors evolve by positive selection.

This notion has been supported and extended by bioinformatic analysis of the tumor-specific mutation spectra in the TP53 gene which show a highly significant excess of non-synonymous mutations over the neutral expectation, suggesting that p53 evolution in tumors is subject to positive selection [ 13 ] as a result of preferential fixation of missense mutations in p53 [ 14 - 16 ].

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