Pluto Bioinformatics

GSE111950: Effect of mutant TRP53 proteins on nutlin-3a treated mouse lymphoma cell lines (RNA-seq)

Bulk RNA sequencing

Mutations in TRP53, prevalent in human cancers, reportedly drive tumorigenesis through dominant-negative-effects (DNE) over wt TRP53 and neomorphic gain-of-function (GOF) effects. We show that five TRP53 mutants do not accelerate lymphomagenesis on a TRP53-deficient background but strongly synergize with c-MYC over-expression. RNA-seq analysis revealed that mutant TRP53 does not globally repress wt TRP53 function but exerts a DNE with disproportionate impact on subsets of wt TRP53 target genes, particularly those involved in DNA repair, proliferation and metabolism. This reveals that the mutant TRP53 DNE drives tumorigenesis by modulating wt TRP53 function in a manner that is advantageous for neoplastic transformation. SOURCE: Gordon,K,Smyth (smyth@wehi.edu.au) - Smyth Walter and Eliza Hall Institute of Medical Research