Hodgkin Lymphoma Monozygotic Triplets Reveal Divergences in DNA Methylation Signatures.

Chuanyou Xia,A Ali Zirakzadeh,Jan Sjöberg,Dawei Xu,Tomas J Ekström,Magnus Björkholm,Hans-Erik Claesson,Ola Winqvist,John Inge Johnsen,Thale Kristin Olsen,Jenny Dahlström,Radwa Almamoun,Klas Strååt,Louise K Sjöholm

doi:10.3389/fonc.2020.598872

Chuanyou Xia, A Ali Zirakzadeh + Show 12 more

Open Access

https://doi.org/10.3389/fonc.2020.598872

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Abstract

We studied DNA methylation profiles in four different cell populations from a unique constellation of monozygotic triplets in whom two had developed Hodgkin Lymphoma (HL). We detected shared differences in DNA methylation signatures when comparing the two HL-affected triplets with the non-affected triplet. The differences were observed in naïve B-cells and marginal zone-like B-cells. DNA methylation differences were also detected when comparing each of the HL-affected triplets against each other. Even though we cannot determine whether treatment and/or disease triggered the observed differences, we believe our data are important on behalf of forthcoming studies, and that it might provide important clues for a better understanding of HL pathogenesis.

Highlights

We previously reported Hodgkin lymphoma (HL) development in two monozygotic triplets where all three were homozygotic through a constitutional deletion in the first intron of the megakaryoblastic leukemia 1 gene (MKL1) [1]
When comparing the methylation profile of each Hodgkin Lymphoma (HL)-triplet against the non-HL-triplet, shared differences in DNA methylation were found in naïve B-cells and marginal zone-like B-cells (Figure 1B)
In the naïve B-cell subpopulation, we found one region on chromosome 18 that differed in DNA methylation

Summary

Introduction

We previously reported Hodgkin lymphoma (HL) development in two monozygotic triplets where all three were homozygotic through a constitutional deletion in the first intron of the megakaryoblastic leukemia 1 gene (MKL1) [1]. The significance of the MKL1 gene deletion in the same set of triplets has recently been studied further by Record et al [2]. We could show that cells from the HL-free sibling had increased cell proliferation, a larger number of hyperploid cells, and further, that cells derived from this triplet were able to form large tumors in vivo. This indicates that the HL-free sibling has pre-malignant cells emerging while the HL-affected triplets do not, possibly due to previous treatment. These data suggest that dysregulated MKL1 activity may participate in DNA Methylation in HL Triplets

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