Mutational Hotspots of TP53 Gene Associated to DNA Damage (pp. 319-342)
Authors: (Angélica Rangel-Lopez, José Ramon Pniagua-Sierra, Unidad de Investigacion Medica en Enfermedades Nefrològicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Mexico)
Abstract: TP53 is the most commonly mutated gene in human cancers, and the p53 protein is a
potent inhibitor of cell growth, arresting cell cycle progression at several points and
inducing apoptosis of cells undergoing uncontrolled growth. The loss of p53 function by
mutation is too common in cancer. However, most natural p53 mutations occur at a late
stage in tumor development, and many clinically detectable cancers have reduced p53
expression but no p53 mutations.
Approximately 90% of the TP53 gene mutations are localized between domains
encoding exons 5 to 8. Much research suggests that TP53 mutations have prognostic
importance and sometimes are a significant factor in clinical Oncology. The presence of
specific p53 mutational hotspots in different types of cancer implicates environmental
carcinogens and endogenous processes in the etiology of human cancer. Oxidative stress
and the generation of reactive species may cause mutations in cancer-related genes, and
affect key regulator proteins of DNA repair, cell cycle, and apoptosis.
This review gives a brief perspective of some of the landmark discoveries in
mutation research. The molecular and biochemical characteristics of TP53 and p53 are
then covered, followed by an overview of how it can be studied in the laboratory.
Finally, the implications of mutational hotspots of TP53 gene at the level of DNA
damage are discussed.