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Methylation of the imprinted GNAS1 gene in cell-free plasma DNA: equal steady-state quantities of methylated and unmethylated DNA in plasma
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Puszyk, William Matthew, Chatha, Kamaljit , Elsenheimer, Selina, Crea, Francesco and Old, R. W. (2009) Methylation of the imprinted GNAS1 gene in cell-free plasma DNA: equal steady-state quantities of methylated and unmethylated DNA in plasma. Clinica Chimica Acta, Vol.400 (No.1-2). pp. 107-110. doi:10.1016/j.cca.2008.10.018 ISSN 0009-8981.
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Official URL: http://dx.doi.org/10.1016/j.cca.2008.10.018
Abstract
Background: Genomic DNA sequences in cell-free plasma are biomarkers of cancer prognosis, where characteristic changes in methylation of turnout suppressor or oncogene DNA regions are indicative of changes in gene activity. Also, cell-free fetal DNA can be distinguished, by its methylation status, from the maternal DNA in the plasma of pregnant women, hence providing DNA biomarkers for the proposed minimally-invasive diagnosis of fetal aneuploidies, including Down's syndrome. However, the production and clearance of cell-free DNA from plasma in relation to its methylation status, are poorly understood processes.
Methods: We studied the methylation status of DNA derived from the imprinted GNAS1 locus, in cell-free plasma DNA of healthy adults. Heterozygotes were identified that carried the SNP rs1800905 in the imprinted region. The parent-of-origin-dependent DNA methylation was analysed by bisulfite conversion, followed by cloning and sequencing.
Results: Genomic DNA molecules derived from both the methylated, maternal, allele and the unmethylated, paternal, allele were found in plasma. Methylated and unmethylated DNA molecules were present in equal numbers.
Conclusions: Our data indicate that the methylation status of a DNA sequence has no effect on its steady state concentration in the cell-free DNA component of plasma, in healthy adults. (C) 2008 Elsevier B.V. All rights reserved.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | R Medicine | ||||
| Journal or Publication Title: | Clinica Chimica Acta | ||||
| Publisher: | Elsevier BV | ||||
| ISSN: | 0009-8981 | ||||
| Official Date: | February 2009 | ||||
| Dates: |
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| Volume: | Vol.400 | ||||
| Number: | No.1-2 | ||||
| Number of Pages: | 4 | ||||
| Page Range: | pp. 107-110 | ||||
| DOI: | 10.1016/j.cca.2008.10.018 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Description: | Available online before print; 30 October 2008 |
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| Funder: | European Commission for the Special Noninvasive Advances in Fetal and Neonatal Evaluation (SAFE) | ||||
| Grant number: | LSHB-CT-2004-503243 |
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