Clinical and molecular subgroups of ependymoma in adulthood: An analysis of the German Glioma Network.

2038 Background: Ependymoma is a subtype of glioma that is rare in adults. Its classification has remained entirely morphological until recently, and surgery and radiotherapy remain the mainstays of treatment. Here we characterized DNA methylation profiles and their clinical correlates in the prospectively assembled cohort of the German Glioma Network. Methods: The GGN cohort was screened for patients diagnosed with myxopapillary ependymoma, subependymoma, classic ependymoma and anaplastic ependymoma for whom clinical data and remaining tumor tissue were available. Tumors were subjected to DNA methylation profiling using the Illumina Infinium HumanMethylation450 BeadChip platform. Molecular data were correlated with morphological tumor and clinical patient characteristics. Results: One hundred and twenty-two ependymoma patients with available tumor tissue were identified. Each adult tumor could be assigned to one of the previously defined methylation classes of ependymoma. Molecular entities of ependymal brain tumors display distinct copy-number variations. PF-EPN-B and ST-EPN-RELA tumors tend to have a worse prognosis than other ependymal subtypes in adults. Conclusions: Molecular classification of adult ependymal methylation subclasses should be implemented in routine diagnostics. Patients with PF-EPN-B and ST-EPN-RELA subtypes might benefit from early treatment beyond surgery.

Epigenome-Wide Association Study of Wellbeing

Wellbeing (WB) is a major topic of research across several scientific disciplines, partly driven by its strong association with psychological and mental health. Twin-family studies have found that both genotype and environment play an important role in explaining the variance in WB. Epigenetic mechanisms, such as DNA methylation, regulate gene expression, and may mediate genetic and environmental effects on WB. Here, for the first time, we apply an epigenome-wide association study (EWAS) approach to identify differentially methylated sites associated with individual differences in WB. Subjects were part of the longitudinal survey studies of the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2002 and 2011. WB was assessed by a short inventory that measures satisfaction with life (SAT). DNA methylation was measured in whole blood by the Illumina Infinium HumanMethylation450 BeadChip (HM450k array) and the association between WB and DNA methylation level was tested at 411,169 autosomal sites. Two sites (cg10845147, p = 1.51 * 10−8 and cg01940273, p = 2.34 * 10−8) reached genome-wide significance following Bonferonni correction. Four more sites (cg03329539, p = 2.76* 10−7; cg09716613, p = 3.23 * 10−7; cg04387347, p = 3.95 * 10−7; and cg02290168, p = 5.23 * 10−7) were considered to be genome-wide significant when applying the widely used criterion of a FDR q value < 0.05. Gene ontology (GO) analysis highlighted enrichment of several central nervous system categories among higher-ranking methylation sites. Overall, these results provide a first insight into the epigenetic mechanisms associated with WB and lay the foundations for future work aiming to unravel the biological mechanisms underlying a complex trait like WB.

Exposure to arsenic and intra-chromosomal instability in blood

The 450k Chip Analysis Methylation Pipeline (ChAMP) is a novel Illumina Infinium HumanMethylation450 BeadChip data processing algorithm that allows the analysis of copy number alterations (CNAs).