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Paediatric leukaemia DNA methylation profiling using MBD enrichment and SOLiD sequencing on archival bone marrow smears

Wong, Nicholas C. L., Meredith, Gavin D., Marnellos, George, Dudas, Miroslav, Parkinson-Bates, Mandy, Halemba, Minhee Suh, Chatterton, Zac, Maksimovic, Jovana, Ashley, David M., Mechinaud, Francoise, Craig, Jeffrey M. and Saffery, Richard 2015, Paediatric leukaemia DNA methylation profiling using MBD enrichment and SOLiD sequencing on archival bone marrow smears, Gigascience, vol. 4, no. 11, pp. 1-6, doi: 10.1186/s13742-015-0050-0.

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Title Paediatric leukaemia DNA methylation profiling using MBD enrichment and SOLiD sequencing on archival bone marrow smears
Author(s) Wong, Nicholas C. L.
Meredith, Gavin D.
Marnellos, George
Dudas, Miroslav
Parkinson-Bates, Mandy
Halemba, Minhee Suh
Chatterton, Zac
Maksimovic, Jovana
Ashley, David M.
Mechinaud, Francoise
Craig, Jeffrey M.
Saffery, Richard
Journal name Gigascience
Volume number 4
Issue number 11
Start page 1
End page 6
Total pages 6
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2015
ISSN 2047-217X
Keyword(s) Childhood leukaemia
DNA methylation
Epigenetics
NGS
SOLiD MBD-Seq
Summary BACKGROUND: Acute Lymphoblastic Leukaemia (ALL) is the most common cancer in children. Over the past four decades, research has advanced the treatment of this cancer from a less than 60% chance of survival to over 85% today. The causal molecular mechanisms remain unclear. Here, we performed sequencing-based genomic DNA methylation profiling of eight paediatric ALL patients using archived bone marrow smear microscope slides. FINDINGS: SOLiD™ sequencing data was collected from Methyl-Binding Domain (MBD) enriched fractions of genomic DNA. The primary tumour and remission bone marrow sample was analysed from eight patients. Four patients relapsed and the relapsed tumour was analysed. Input and MBD-enriched DNA from each sample was sequenced, aligned to the hg19 reference genome and analysed for enrichment peaks using MACS (Model-based Analysis for ChIP-Seq) and HOMER (Hypergeometric Optimization of Motif EnRichment). In total, 3.67 gigabases (Gb) were sequenced, 2.74 Gb were aligned to the reference genome (average 74.66% alignment efficiency). This dataset enables the interrogation of differential DNA methylation associated with paediatric ALL. Preliminary results reveal concordant regions of enrichment indicative of a DNA methylation signature. CONCLUSION: Our dataset represents one of the first SOLiD™MBD-Seq studies performed on paediatric ALL and is the first to utilise archival bone marrow smears. Differential DNA methylation between cancer and equivalent disease-free tissue can be identified and correlated with existing and published genomic studies. Given the rarity of paediatric haematopoietic malignancies, relative to adult counterparts, our demonstration of the utility of archived bone marrow smear samples to high-throughput methylation sequencing approaches offers tremendous potential to explore the role of DNA methylation in the aetiology of cancer.
Language eng
DOI 10.1186/s13742-015-0050-0
Field of Research 111499 Paediatrics and Reproductive Medicine not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, BioMed Central
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30074219

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.