Different p53 mutations play distinct roles throughout carcinogenesis
Our new preprint on the dynamics and impact of p53 mutation at different stages of carcinogenesis reveals new insights into the role of this ubiquitous tumour suppressor (https://www.biorxiv.org/content/10.1101/2022.02.03.478951v1). In healthy human tissues p53 mutation is commonly observed, whilst in tumours we observe both mutation of one allele, and loss of the second unmutated allele.
Our work here shows that the initial p53 mutation has a fitness advantage, enabling it to spread throughout the tissue. In contrast, the loss of the second allele offers no further advantage but enables the genomic instability necessary for tumour development. We argue that this neutrality acts as a bottleneck for cancer development, effectively reducing the incidence of the disease.