Investigating the Epigenomic Effects of Genetic Alterations in High-Risk Neuroblastoma
Background
The Maris Lab studies the pediatric cancer neuroblastoma, which is a cancer of nerve cells that develop outside of the brain. Although the 5-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 tumor formation in 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, helping turn genes on or off. Our laboratory has previously identified single nucleotide polymorphisms (SNPs, alterations) in non-coding gene regions that are significantly associated with tumor formation. Those genes include LMO1, HACE1, HSD17B12, LIN28B, CPZ, CASC15, MLF1, TP53 and BARD1.
Project Goal
In this project, we will utilize recently-developed, advanced algorithms to determine whether tumor-associated SNPs in these genes differentially recruit transcription factors and enhancers to dysregulate normal gene expression. Understanding how such genetic alterations influence recruitment of proteins is one key to understanding the mechanism of tumor formation.
Mentored by Dr. Jo Lynne Harenza
Children’s Hospital of Philadelphia, Philadelphia, PA
