RECQL4 Expression in RTS Patient Cells

Background

Our laboratory is interested in finding better treatments for osteosarcoma (OS), the most common malignant primary bone tumor in children and adolescents. Survival rates for patients with OS have not changed for more than 30 years. We have been studying a rare genetic disorder called Rothmund-Thomson syndrome (RTS) as a model for OS development, where 2/3 of patients have germline mutations in a gene called RECQL4 (Type II RTS). These patients have an extremely high and specific risk for developing OS.

The other 1/3 of patients (Type I RTS) do not carry mutations in RECQL4 and do not develop OS. Type I patients may have mutations in other genes that have not yet been identified. By studying RTS as a model for OS development, we hope to decipher other molecules that interact with RECQL4 in order to find targetable pathways for therapy of OS.

Project Goal

This project will study the expression of RECQL4 in RTS patient samples. We expect to detect changes in RECQL4 levels in Type II RTS patients. We will perform genotype-phenotype correlations with the various clinical findings in these patients. This information will be useful in counseling families, e.g., on the risk of developing OS.

If Type I RTS patients are found to have changes in RECQL4 expression, this would suggest that the gene(s) affected in Type I interact with the RECQL4 pathway and will provide important preliminary data to further investigate those other pathways as they relate to OS.