Identification of LMO1 Binding Partners and Their Role in Neuroblastoma Tumorigenesis

Background

The Maris Lab studies a pediatric cancer called neuroblastoma, which is a cancer of nerves that develop outside of the brain. Commonly, it presents as a tumor mass in the abdomen. Although the five-year survival rate for children in the low- and intermediate-risk groups ranges over 95%, children with high-risk disease have only a 40% likelihood of survival. Furthermore, high-dose chemotherapy increases risk of infertility, severe hearing loss, cardiac toxicity, and/or secondary cancers. Therefore, we urgently need to identify new therapies for children with high-risk disease. In each child's tumor, we detect very few mutations within the portion of genes that codes for functional proteins (exons). This means that the remaining mutations responsible for neuroblastoma likely reside within the non-coding region of the tumor's DNA, either within genes (introns) or between genes. We now know that these non-coding regions play important roles in gene regulation, as they help turn genes on or off. The Maris Lab previously identified a mutation in an intron of the LMO1 gene which increases its expression and an individual's susceptibility to developing neuroblastoma.

Project Goal

In order to investigate how LMO1 promotes this cancer, we will be developing a molecule that binds specifically to the LMO1 protein. This will allow us to capture only LMO1 and any other proteins to which it is bound. We hope this new tool will allow us to identify LMO1's binding partners and shed light on how high levels of this oncogene lead to the development of neuroblastoma.