A Characterization of TP53 Mutations Among Pediatric Osteosarcoma Cases

Background

Knowledge of the genetic contributions to osteosarcoma (OS) susceptibility is critical for improving patient outcomes by enabling early detection and disease prediction. Brandon's project will be to expand the literature on an important gene, TP53, by characterizing the distribution of its variants among osteosarcoma cases and further examining its relationship to genetically-determined growth.

Project Goal

Specifically, Brandon will describe the spectrum of germline TP53 variants and their distributions among 234 pediatric OS cases collected and sequenced by Dr. Spector as part of the Children's Oncology Group “Genetic Epidemiology of Osteosarcoma” (AEPI05N2) study.  Brandon will characterize the spectrum of TP53 variants by its association with Li-Fraumeni syndrome, predicted pathogenicity, frequency throughout the world and the function of the domain affected. The results of this characterization will be compared to two recent series aimed at further detailing germline TP53 variants among childhood cancers.

He will also will characterize the distribution of pathogenic TP53 variants between individuals with a higher and lower genetic potential for height. We hypothesize that osteosarcoma cases with less genetic potential for height were more likely to develop osteosarcoma as a result of an underlying genetic predisposition, whereas those individuals with a greater genetic potential for height were more likely to develop osteosarcoma as a result of 'bad luck' from relatively more cellular divisions during growth. Therefore, we expect to observe a higher frequency of pathogenic TP53 in individuals with less genetic height potential.