Examining the DNA Methylation Profile of Childhood Solid Tumors to Identify Novel Therapeutically Targeted Sites

Abstract ID 53598 Poster Board 438 Solid tumors in children represent approximatively 30% of all pediatric cancers. The most prevalent types are Wilms tumor, retinoblastoma, neuroblastoma, and Ewing’s sarcoma. The literature suggested that there is a degree of similarity between these conditions (such as age of diagnosis, prognosis, etc.), indicating that they may share a similar pathogenesis. The objective of our study was to investigate the DNA methylation profile of common childhood solid tumors in order to find a common signature that can be used to understand the underlying common molecular mechanism and to identify new pharmacological targets. This was an in silico study which used publicly available data from a DNA methylation array. Illumina 450K array datasets of the four conditions were downloaded from the GEO data repository and processed on RStudio. Differentially methylated sites were selected based on scoring Student’s t-test P-value ≤ 0.001 and a methylation difference (delta beta) ≥ 20%. Differentially methylated genes were defined as genes having at least two differentially methylated sites according to the human GRCh37/hg19 annotation. The study included 82 controls and 357 cases of childhood solid tumors. The analysis revealed that there were 13,472 novel differentially methylated sites that shared a common methylation profile between all the tumors. Using the hierarchical clustering method, the differentially methylated sites properly clustered all cases of childhood solid tumors. In addition, the analysis identified 17 differentially methylated genes that were involved in cell-cell communication, signal transduction and immune system pathways. The novel discovery of the common differentially methylated sites and genes among common childhood solid tumors provided an insight towards understanding their shared molecular pathogenesis. In addition, the identified candidate genes can be used as biomarkers for the clinical diagnosis and as therapeutic pharmacoepigenomic targets of childhood solid tumors.