Since many sarcomas can be resistant to adjuvant therapies, it is important to identify inherited genetic markers to detect individuals with an increased risk of developing sarcomas, and therefore to increase the likelihood of detecting low-grade sarcomas, while curative surgical intervention is still possible. The awarded grant "Evaluation of Genetic Biomarkers in the p53 Pathway for Sarcoma Susceptibility" will look at single nucleotide polymorphisms (SNPs) in the p53 pathway to deepen our understanding of the molecular defects that disrupt the p53 pathway in the onset of sarcoma and identify genetic variants that predict increased risk of developing sarcoma, enabling closer monitoring of individuals with these SNPs and therefore earlier treatment should they develop sarcoma.
The Liddy Shriver Sarcoma Initiative, founded in 2003, is a charity whose mission is to improve the quality of life for people dealing with sarcomas around the world. It aims to increase public awareness of sarcoma, raises funds to award research grants, and provides support to sarcoma patients, their families, and medical professionals.
Figure1: The different alleles of MDM2 SNP309: The different alleles of MDM2 SNP309 are subject to differential transcriptional activation by the transcription factor Sp1, thereby resulting in differential cellular levels of MDM2 and p53 activity. These differences in transcriptional regulation of MDM2 significantly affect p53's role in cancer susceptibility, progression and survival in many cancer types. Indeed, MDM2 SNP309 has been clearly shown to affect sarcoma in mouse and man.