Validation of the MethylationEPIC BeadChip for fresh-frozen and formalin-fixed paraffin-embedded tumours (450K)

DNA methylation is the most studied epigenetic modification due to its role in regulating gene expression and aberrations in methylation involved in the pathogenesis of cancer and several diseases. The method of choice to evaluate genome-wide methylation has been the Illumina HumanMethylation450 BeadChip (450K), but it was recently replaced with the MethylationEPIC BeadChip (EPIC). We therefore sought to validate the EPIC array in comparison to the 450K array for both fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) pediatric brain tumors. We also performed analysis on the EPIC array with paired FF and FFPE samples, to adapt to a clinical setting where FFPE is routinely used. Further, we compared two restoration methods, REPLI-g and Infinium, for FFPE-derived DNA on the EPIC array. 9 fresh-frozen (FF) pediatric brain tumor samples (tumors T01-T09) were processed on the Illumina 450K and EPIC array to compare the platforms. 9 formalin-fixed paraffin-embedded (FFPE) samples paired to the FF samples (tumors T01-T09) were analyzed on the EPIC array to assess the correlation between FF and FFPE and thereby the suitability of the array in a clinical setting (FFPE samples). Four of the FFPE samples (tumors T01, T06, T08, T09) were restored with both the REPLI-g and Infinium protocol to enable comparison between the methods. Three FFPE samples (tumors T10-T12), restored with REPLI-g, were analyzed with the 450K as well as the EPIC array to compare the platforms for FFPE samples.