Genomic characterization of a TP53tandem duplication in a pediatric patient with Li-Fraumeni syndrome

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome that affects both pediatric and adult patients. Individuals with LFS are at an increased risk of developing various types of cancer over their lifetime including soft tissue sarcomas, osteosarcomas, breast cancer, leukemia, brain tumors, and adrenocortical carcinoma. Heterozygous germline pathogenic variants in the tumor suppressor TP53 gene are the known causal genetic defect associated with LFS. Missense substitutions that occur in the highly conserved DNA binding domain of the protein are the most common alterations, followed by nonsense and splice site variants.