A Bioinformatics Analysis of the Transcription Interactions of Mutant p53 with Other Oncogenes

Abstract

Several studies have shown that the evolutionary conserved tumor suppressive p53 protein upon undergoing mutations acquires new oncogenic functions. Termed gain of function (GOF) mutant p53 (mtp53), this mutant gene interacts with other genes and activates their transcription to promote metastasis, contrary to its earlier suppressive functions. While focus on p53-centric studies has increased since the turn of the century, progress has been slow. The genes associated with mtp53 in carrying out said functions remain to be accounted for or knowledge on them is incomplete at best. This research aims to use computational databases and platforms to predict some of these transcriptional hotspots. It is reported that breast cancer (BRCA), uterine cancer and colon cancer particularly show high expression of the gene. In BRCA, p53 has the highest expression in Triple Negative Breast Cancer (TNBC) and HER2+ subtypes, both of them invasive cancers. p53 is also reported to be an essential gene for TNBC cell lines. It is also found that mtp53 BRCA has overexpression of several oncogenes like S100A9, PSAT1, LCN2, etc., many of which have preexisting transcription associations with p53. TP53 is found to be most susceptible to PROTACS, while the other genes have shown a variety of results, ranging from antibodies to small molecules. On the basis of their over-expression in BRCA with TP53 mutant tumors and transcriptional history with p53, it is hypothesized that these genes form interactions with mtp53 in order to promote tumorigenesis.

Keywords: TP53, mtp53, GOF, BRCA, bioinformatics, over-expression, under-expression