Genome-wide methylation analysis of blood cells from homozygotic triplets

We report genome-wide methylation profiles of four blood cell populations from homozygotic triplets, of which two has Hodgkin lymphoma (triplets A and B) and one does not (triplet C). DNA was isolated from CD34+ cells, marginal zone-like B cells, naïve B cells and switched memory B cells and analyzed using the Illumina EPIC platform. We previously reported Hodgkin lymphoma development in two triplets where all three were homozygotic and had a constitutional deletion in the first intron of the MKL1 (megakaryoblastic leukemia 1) gene; see Bjorkholm et al, Blood 2013;121:4807. The significance by the MKL1 gene deletion in the same set of homozygotic triplets has recently been studied further by Record et al (Haematologica 2019, PMID 31582539), whose investigations suggest that dysregulated MKL1 activity may participate in B cell transformation and HL pathogenesis. It is well recognized that first degree relatives of HL patients carry an increased risk of developing the disease. In this study, we aimed to evaluate the genome-wide DNA methylation profile of several B cell populations as well as CD34+ cells in the triplets. Bisulphite treated DNA from a total of 12 samples (4 cell populations from 3 triplets) were hybridized to the Illumina Infinium MethylationEPIC_v-1-0 beadchip with 850.000 CpG site-specific probes.