This study aimed to characterize the TP53 mutational spectrum in patients suspected to have LFS in Portugal and to evaluate the influence of the MDM2-SNP309 and TP53-72Arg variants and of telomere length on age of tumor onset.
The higher prevalence of MDM2 SNP309 homozygous G/G carriers in the TP53-negative group suggests that this allele contributes to cancer susceptibility in LFS and LFS-related families.
The higher prevalence of MDM2 SNP309 homozygous G/G carriers in the TP53-negative group suggests that this allele contributes to cancer susceptibility in LFS and LFS-related families.
Recently, a single-nucleotide polymorphism in the MDM2 promoter (SNP309) has been found to lower the age of onset of tumors and increase the occurrence of multiple primary tumors in Li-Fraumeni syndrome, and accelerate the development of sporadic adult soft tissue sarcoma.
Previous studies have highlighted the contribution of the common functional polymorphisms p53 p.Arg72Pro and MDM2 309SNP to the risk of both common cancers and Li-Fraumeni syndrome.
Interestingly, the p53 mutation found in this LFS family is localized to the p53 region that we have recently identified as necessary for Mdm2-mediated p53 degradation.
In contrast with several case-series studies, the interaction between MDM2 SNP309 and TP53 mutation was not statistically significant in our LFS family cohort.
Although it needs further evaluations, obtained results strengthen the role of MDM2 SNP309 as a genetic factor in hereditary predisposition to cancer, so improving LFS Suggestive patients management.
Although no other gene has been found in Li-Fraumeni syndrome, recent results show that the functional effects of particular mutations, polymorphisms in TP53 or in regulators such as MDM2 (murine double minute 2), variations in DNA copy number and variations in telomere length, have a strong impact on individual risk and on tumor patterns.
A single-nucleotide polymorphism (SNP) in the promoter of the MDM2 gene, SNP309 (a T-->G change), was recently implicated in the early onset of cancer in individuals with Li-Fraumeni syndrome and of sporadic soft-tissue sarcoma.
MDM2 SNP309 is associated with younger age of tumor onset in patients with Li-Fraumeni syndrome, and TP53 codon 72 polymorphism decreases its apoptotic potential.