Maternal folate genes and aberrant DNA hypermethylation in pediatric acute lymphoblastic leukemia

PloS One
Jeremy M SchrawMichael E Scheurer

Abstract

There is evidence that maternal genotypes in folate-related genes are associated with pediatric acute lymphoblastic leukemia (ALL) independent of offspring genotype. We evaluated the relationship between maternal genotypes in methionine synthase (MTR) and DNA methylation status in ALL to better characterize the molecular mechanism underlying this association. We obtained bone marrow samples from 51 patients with ALL at diagnosis and from 6 healthy donors. Mothers of patients provided a saliva sample and were genotyped at 11 tagSNPs in MTR. DNA methylation was measured in bone marrow mononuclear cells of patients and six healthy marrow donors. We used hierarchical clustering to identify patients with a hypermethylator phenotype based on 281 differentially methylated promoter CpGs. We used logistic regression to estimate the effects of maternal genotype on the likelihood of DNA hypermethylation in ALL and Ingenuity Pathway Analysis to identify networks enriched for differentially methylated genes. Twenty-two cases (43%) demonstrated promoter hypermethylation, which was more frequent among those with ETV6-RUNX1 fusion and initial white blood cell count < 50 x 109/L. Maternal rs12759827 was associated with aberrant DNA methylation ...Continue Reading

References

Mar 1, 1997·Current Biology : CB·S U KassA P Wolffe
May 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·A M FordM Greaves
Nov 7, 1999·Lancet·J L WiemelsM F Greaves
Dec 26, 2001·Nucleic Acids Research·Ron EdgarAlex E Lash
Sep 3, 2003·Nature Reviews. Cancer·Mel F Greaves, Joe Wiemels
Aug 18, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jose Roman-GomezAntonio Torres
Feb 23, 2007·Clinical Pharmacology and Therapeutics·Y I GohG Koren
Jan 12, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ching-Hon PuiRobert J Arceci
Mar 28, 2012·The Journal of Reproduction and Development·Shuntaro IkedaShinichi Kume
Apr 26, 2012·Epigenetics : Official Journal of the DNA Methylation Society·Nicholas C WongRichard Saffery
Sep 4, 2012·Cancer Causes & Control : CCC·Philip J LupoMichael E Scheurer
Nov 1, 2012·British Journal of Haematology·Juan SandovalManel Esteller
May 30, 2013·Nature Genetics·UNKNOWN GTEx Consortium
Nov 11, 2015·BMC Genomics·Paul YousefiNina Holland

❮ Previous
Next ❯

Citations

Jun 24, 2021·Biology of Reproduction·Sean M CullenMatthew Smith-Raska

❮ Previous
Next ❯

Methods Mentioned

BETA
methylation profiling
genotyping
MCA-Seq

Software Mentioned

Ingenuity Pathway Analysis
UCSC Genome Browser
IPA

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Related Papers

International Journal of Cancer. Journal International Du Cancer
Elizabeth MilneBruce K Armstrong
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Meng Hua TaoJo L Freudenheim
© 2022 Meta ULC. All rights reserved