Analysis of Tumor Methylation Quantitative Trait Loci in Pediatric Cancer Patients with Central Nervous System Tumors

Abstract

While many adult cancers are characterized by a large number of somatic mutations, pediatric cancers tend to be associated with a greater prevalence of germline mutations in cancer predisposition genes. However, the mechanisms through which these germline variants impact tumor progression remain poorly understood. The goal of this project is to uncover the genetic basis for epigenetic changes potentially impacting tumor development by integrating germline genotypic data with tumor methylation data through a tumor methylation quantitative trait loci (tumor meQTLs) framework. Tumor meQTLs are germline genomic loci at which different genotypes are associated with differences in methylation levels at nearby sites in the tumor sample. To map the QTLs, I used pre-processed and normalized methylation data and merged genotype files from 528 pediatric cancer patients with central nervous system tumors. Ultimately, 5,889 significant tumor meQTL associations were identified. A couple of these QTLs were found to be within known medulloblastoma predisposition genes, however more work must be done to contextualize this list of associations.No embargoAcademic Major: Data Analytic