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

Paola Monti, Paola Menichini, Andrea Speciale, Giovanna Cutrona, Franco Fais, Elisa Taiana, Antonino Neri, Riccardo Bomben, Massimo Gentile, Valter Gattei, Manlio Ferrarini, Fortunato Morabito, Gilberto Fronza

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Article number593383
JournalFrontiers in Oncology
Publication statusPublished - Oct 28 2020


  • chronic lymphocytic leukemia
  • clinical impact
  • P53 protein function
  • reactivation of P53
  • TP53 mutations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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