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DNA methylation at birth in monozygotic twins discordant for pediatric acute lymphoblastic leukemia

Author

Listed:
  • Eric M. Nickels

    (Cancer and Blood Disease Institute
    University of Southern California)

  • Shaobo Li

    (University of Southern California)

  • Swe Swe Myint

    (University of Southern California)

  • Katti Arroyo

    (University of Southern California)

  • Qianxi Feng

    (University of Southern California)

  • Kimberly D. Siegmund

    (University of Southern California)

  • Adam J. de Smith

    (University of Southern California)

  • Joseph L. Wiemels

    (University of Southern California)

Abstract

Aberrant DNA methylation constitutes a key feature of pediatric acute lymphoblastic leukemia at diagnosis, however its role as a predisposing or early contributor to leukemia development remains unknown. Here, we evaluate DNA methylation at birth in 41 leukemia-discordant monozygotic twin pairs using the Illumina EPIC array on archived neonatal blood spots to identify epigenetic variation associated with development of pediatric acute lymphoblastic leukemia, independent of genetic influence. Through conditional logistic regression we identify 240 significant probes and 10 regions associated with the discordant onset of leukemia. We identify a significant negative coefficient bias, indicating DNA hypomethylation in cases, across the array and enhanced in open sea, shelf/shore, and gene body regions compared to promoter and CpG island regions. Here, we show an association between global DNA hypomethylation and future development of pediatric acute lymphoblastic leukemia across disease-discordant genetically identical twins, implying DNA hypomethylation may contribute more generally to leukemia risk.

Suggested Citation

  • Eric M. Nickels & Shaobo Li & Swe Swe Myint & Katti Arroyo & Qianxi Feng & Kimberly D. Siegmund & Adam J. de Smith & Joseph L. Wiemels, 2022. "DNA methylation at birth in monozygotic twins discordant for pediatric acute lymphoblastic leukemia," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33677-z
    DOI: 10.1038/s41467-022-33677-z
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    1. Jenny Dongen & Scott D. Gordon & Allan F. McRae & Veronika V. Odintsova & Hamdi Mbarek & Charles E. Breeze & Karen Sugden & Sara Lundgren & Juan E. Castillo-Fernandez & Eilis Hannon & Terrie E. Moffit, 2021. "Identical twins carry a persistent epigenetic signature of early genome programming," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Bonnie R. Joubert & Herman T. den Dekker & Janine F. Felix & Jon Bohlin & Symen Ligthart & Emma Beckett & Henning Tiemeier & Joyce B. van Meurs & Andre G. Uitterlinden & Albert Hofman & Siri E. Håberg, 2016. "Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns," Nature Communications, Nature, vol. 7(1), pages 1-8, April.
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