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Leukemia & Lymphoma Volume 60, 2019 - Issue 6
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Original Article

DNA methylation patterns of adult survivors of adolescent/young adult Hodgkin lymphoma compared to their unaffected monozygotic twin

Jun WangDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA;
,
David Van Den BergDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA;
,
Amie E. HwangDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA;
,
Daniel WeisenbergerNorris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA;
,
Timothy TricheDepartment of Translational Genomics, University of Southern California, Los Angeles, CA, USA; ;Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA;
,
Bharat N. NathwaniDepartment of Pathology, City of Hope National Medical Center, Duarte, CA, USA;
,
David V. ContiDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA;
,
Kim SiegmundDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA;
,
Thomas M. MackDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA; ;Department of Pathology, University of Southern California, Los Angeles, CA, USA;
,
Steve HorvathDepartment of Biostatistics, University of California at Los Angeles, Los Angeles, CA, USA
&
Wendy CozenDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA, USA; ;Department of Pathology, University of Southern California, Los Angeles, CA, USA; Correspondence[email protected]
 show all
Pages 1429-1437 | Received 16 Jun 2018, Accepted 02 Oct 2018, Published online: 22 Jan 2019
 
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Abstract

DNA methylation (DNAm) silences gene expression and may play a role in immune dysregulation that is characteristic of adolescent/young adult Hodgkin lymphoma (AYAHL). We used the Infinium HumanMethylation27 BeadChip to quantify DNAm in blood (N = 9 pairs, mean age 57.4 y) or saliva (N = 36 pairs, mean age 50.0 y) from long-term AYAHL survivors and their unaffected co-twins. Epigenetic aging (DNAm age) was calculated using previously described methods and compared between survivors and co-twins using paired t-tests and analyses were stratified by sample type, histology, sex, age at sample collection and time since diagnosis. Differences in blood DNAm age were observed between survivors and unaffected co-twins (64.1 vs. 61.3 years, respectively, p = .04), especially in females (p = .01); no differences in saliva DNAm age were observed. Survivors and co-twins had 74 (in blood DNA) and 6 (in saliva DNA) differentially methylated loci. Our results suggest persistent epigenetic aging in AYAHL survivors long after HL cure.

Acknowledgements

This work was supported by the National Institutes of Environmental Health Science (1R01ESO15150-01 to TMM) and from the National Cancer Institute (1R03CA110836 to WC), the Leukemia Lymphoma Society (TRP-6137-07 to WC), the Department of Defense Peer-Reviewed Medical Research Program (PR054600 to WC), and the American Society of Hematology Bridge Grant Program (to WC). We would like to thank the participants and staff of the International Twin Registry at University of Southern California for their valuable contributions. The authors assume full responsibility for analyses and interpretation of these data.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10.1080/10428194.2018.1533128.

Data availability

The data that support the findings of this study are available from the corresponding author, W.C., upon reasonable request.

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