Research Abstracts Online
January - December 2011
University of Minnesota Twin Cities
PI: Jenny Poynter
DNA Methylation in Pediatric Germ Cell Tumors
Pediatric germ cell tumors (GCTs) are heterogeneous and grouped together due to the presumed common cell of origin, the primordial germ cell. Generally, GCTs are grouped into two broad classes based on degree of differentiation: the germinomas, comprising testicular seminomas and ovarian dysgerminomas, and the nonseminomas, comprising yolk sac tumors, embryonal carcinomas, choriocarcinomas, and teratomas. Aberrant DNA methylation has been implicated in cancer etiology, and may be especially relevant in GCTs due to the extensive epigenetic reprogramming that occurs in the germ line and early embryo during normal development. This project includes DNA methylation in 52 pediatric GCTs; methylation differences in the three main histologic subtypes (yolk sac tumors, dysgerminomas, and teratomas) are evaluated using unsupervised hierarchical clustering with the Manhattan metric and average linkage. A locus-by-locus approach is used to identify genes that were differentially methylated by tumor histology using a generalized linear model and accounted for multiple testing by controlling the false-discovery rate. Ingenuity Pathway Analysis will be used to identify pathways that are enriched in this dataset. Understanding methylation patterns in pediatric GCTs, overall and by histologic type, may identify the developmental stage at which the tumor arose. This knowledge in turn may identify the at-risk period when environmental exposures are most harmful.