# Heterogeneity of TP53 Mutations and P53 Protein Residual Function in Cancer: Does It Matter?

## TL;DR

This paper reviews how TP53 mutations affect P53 protein function in cancer, focusing on their clinical implications, especially in Chronic Lymphocytic Leukemia.

## Contribution

The paper provides a focused review on the functional and clinical impact of TP53 mutations in Chronic Lymphocytic Leukemia.

## Key findings

- TP53 mutations are common in cancer and often affect the DNA binding domain of the P53 protein.
- Mutant P53 proteins can retain partial function, influencing cancer prognosis and treatment decisions.
- In Chronic Lymphocytic Leukemia, TP53 mutations are critical for determining therapy strategies.

## Abstract

The human TP53 locus, located on the short arm of chromosome 17, encodes a tumour suppressor protein which functions as a tetrameric transcription factor capable of regulating the expression of a plethora of target genes involved in cell cycle arrest, apoptosis, DNA repair, autophagy, and metabolism regulation. TP53 is the most commonly mutated gene in human cancer cells and TP53 germ-line mutations are responsible for the cancer-prone Li-Fraumeni syndrome. When mutated, the TP53 gene generally presents missense mutations, which can be distributed throughout the coding sequence, although they are found most frequently in the central DNA binding domain of the protein. TP53 mutations represent an important prognostic and predictive marker in cancer. The presence of a TP53 mutation does not necessarily imply a complete P53 inactivation; in fact, mutant P53 proteins are classified based on the effects on P53 protein function. Different models have been used to explore these never-ending facets of TP53 mutations, generating abundant experimental data on their functional impact. Here, we briefly review the studies analysing the consequences of TP53 mutations on P53 protein function and their possible implications for clinical outcome. The focus shall be on Chronic Lymphocytic Leukemia (CLL), which also has generated considerable discussion on the role of TP53 mutations for therapy decisions.