GENOME STRUCTURE AND FUNCTION MUTATIONAL HOTSPOTS IN THE P53 GENE REVEALED BY CLASSIFICATION ANALYSIS

Motivation: The p53 protein is a multifunctional transcription factor: it regulates cell cycle progression and interacts with several key proteins involved in DNA replication, transcription, repair and apoptosis. Nearly 60 % of all human cancers of different origins are accompanied by mutational events in the p53 gene. Results: We compared the mutational spectra in the p53 gene from different tumors, observed in germline cancer-prone families, in tumors of different histogenesis and their derived cell lines and second examine the p53 hotspots map in the evolutionary perspective. While spectra from different solid tumors share common hotspots with the germline spectrum (CpG sites), they also contain unique sets of new hotspots that are not observed in the germline spectrum (new CpG and non-CpG sites). Our analysis suggested that the distribution of hotspots in the p53 gene could be influenced by cell growth conditions, as well as the specificity of the mutagenesis and the bulk hotspots analysis do not take into account these differences