TP53 gene

TP53 is a tumour suppressor gene that causes Li-Fraumeni syndrome and affects adults and children

• highly penetrant gene predisposes for a wide spectrum of tumours, including sarcomas, adrenocortical carcinomas, brain cancer, and very early onset breast cancer
  • TP53 gene provides instructions for making a protein called tumor protein p53. This protein acts as a tumor suppressor
  • majority of TP53 mutations result in the substitution of single aminoacids in the central region of the p53 protein, generating a spectrum of variants ('mutant p53s', for short)
    • these mutants lose the normal p53 oncosuppressive functions to various extents but can also acquire oncogenic properties by gain-of-function mechanisms
  • most cancers are manifested from birth through late adulthood
  • taking into account the tissue and organ specificity of tumors, breast cancer is the single most frequent event in Li-Fraumeni syndrome, accounting for >25% of all tumors in affected families
    
    
• TP53 mutation carriers face a lifetime cancer risk that exceeds 90%
  
  
• patients with Li-Fraumeni syndrome have an abnormal response to low-dose radiation
  • radiation in these patients should be avoided as a therapeutic approach because of the increased secondary tumour risk
    
    
• breast cancer is the most frequent malignancy among female TP53 mutation carriers, with approximately 5% of these cases being diagnosed before the age of 30
  • Li-Fraumeni syndrome accounts for a small fraction of breast cancer cases (approximately 0.1%)
    • however TP53 mutation carriers have from an 18- to 60-fold increased risk for early onset breast cancer (diagnosed before the age of 45) when compared to the general population

Reference:

• 1) Apostolou P, Fostira F. Hereditary breast cancer: the era of new susceptibility genes.Biomed Res Int. 2013;2013:747318.
• 2) Walerych D et al. The rebel angel: mutant p53 as the driving oncogene in breast cancer. Carcinogenesis. 2012 Nov;33(11):2007-17.