Identification of methylated loci involved in survival among pediatric medulloblastoma patients
There are over 120 different types of brain tumors and, of these, medulloblastoma is the most frequent, affecting approximately 500 children in the US annually. Though significant prognostic improvements have been made, there is little evidence as to why survival varies among children diagnosed with medulloblastoma. The aim of this study was to determine whether differentially methylated loci in the gene ERCC2 were associated with survival among those with pediatric medulloblastoma. The study population included 88 medulloblastoma patients that were under 18 years of age and recruited from Texas Children's Cancer Center from March 1987-July 2009. Peripheral blood samples from each patient were previously collected and bisulfite treatment was completed on all extracted blood. Methylation data gathered from the Illumina Infinium Human Methylation 450 Beadchip was put through various quality control platforms and, in the end, sixteen promoter-associated probes passed quality control and were used in this analysis. Logistic regression was run on the data after dichotomizing methylation values for each probe at the median and the false-discovery rate was used to correct for multiple comparisons. Linear regression was then run using continuous methylation data. Survival analysis using Kaplan-Meier curves to compare five-year survival between those with high methylation and those with low methylation at each probe was performed and, subsequently, log-rank p-values were calculated to allow for comparison of these curves. This study found that most ERCC2 probes were not associated with survival. However, high methylation in the cg02257300 probe was found to be associated with decreased survival. This association remained suggestive after correcting for multiple comparisons and is consistent with existing literature. These findings suggest that the use of peripheral blood samples at diagnosis to identify increased methylation in the cg02257300 probe might allow for directed therapy in pediatric medulloblastoma patients. ^
Banfield, Emilyn, "Identification of methylated loci involved in survival among pediatric medulloblastoma patients" (2015). Texas Medical Center Dissertations (via ProQuest). AAI1597017.