Abstract 155: A comparison of DNA methylation in identical twins discordant for Hodgkin lymphoma

Abstract

Abstract DNA methylation is an epigenetic change that may affect gene expression. Environmental determinants are largely unknown but strongly suspected. Because twins are matched on genome and to some extent, early life exposures, a comparison of DNA methylation between twins is of more interest than one between unrelated individuals. To evaluate the possibility of an association between DNA methylation and young adult Hodgkin lymphoma (HL), DNA samples from blood or saliva were collected from both members of 25 identical twin pairs in whom one twin had developed HL prior to age 50 (discordant pairs). The median time since diagnosis was 16 years. DNA methylation status at 27,578 loci in 14,475 genes was measured in each sample using the Illumina Infinium methylation assay. We measured any difference (< or > 0) in the level of DNA methylation at each locus between the case and the unaffected co-twin and applied a paired t-test. The overall pattern indicated that cases had higher levels of DNA methylation at loci with lower average DNA methylation levels, but the reverse was true at loci with higher overall levels of DNA methylation (e.g., here the cases had lower levels). With respect to specific loci, the HL case consistently had a higher level of DNA methylation compared to his/her unaffected co-twin at locus cg24693053 in the MFSD7 (major facilitator superfamily domain containing 7) gene in 22/25 pairs; this was also the locus with the most significant p-value (p= 0.0000332). Twenty-two out of 25 cases had a lower level of DNA methylation than their unaffected co-twin at loci cg17385448 in the AGMAT (Agmatine ureohydrolase [agmatinase]) gene (p= 0.0001587) and cg09809672 in the EDARADD (EDAR-associated death domain) gene (p= 0.003775846). Seventeen out of 19 cases with the nodular sclerosis subtype had consistently higher DNA methylation levels at 9 loci and lower levels at 7 loci compared to their unaffected co-twin (binomial test p=0.0007). There was no overall effect on the pattern of methylation by time since diagnosis. We observed suggestive differences in DNA methylation levels in normal peripheral blood mononuclear cells collected from young adult HL patients in remission relative to their unaffected identical co-twins. The differences may have resulted from HL disease or treatment, or could have pre-dated the diagnosis. The results are compatible with a role of the cumulative environment on DNA methylation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 155.