Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12694
Title: Paediatric leukaemia DNA methylation profiling using MBD enrichment and SOLiD sequencing on archival bone marrow smears.
Authors: Wong, Nicholas Cl;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
Affiliation: Cancer and Disease Epigenetics Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, 3052 Victoria Australia ; Department of Paediatrics, The University of Melbourne, Children's Hospital, Flemington Road, Parkville, 3052 Victoria Australia ; Translational Genomics and Epigenomics Research Group, Ludwig Cancer Research, Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Burgundy Street, Heidelberg, 3084 Victoria Australia ; Pacific Edge Limted, 84 St David Street, Dunedin 9016, New Zealand.
Life Technologies, Carlsbad, 92008 CA USA.
Life Technologies, Carlsbad, 92008 CA USA ; Current Address: Science Division Informatics Group, Faculty of Arts and Sciences, Harvard University, MA 02138, Cambridge USA.
Cancer and Disease Epigenetics Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, 3052 Victoria Australia.
Bioinformatics Group, Quantitative Sciences Core, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, 92008, Parkville, 3052 Victoria Australia.
Andrew Love Cancer Centre, Deakin Universit, Swanston Street, Geelong, 3220 Victoria Australia.
Children's Cancer Centre, Royal Children's Hospital, Flemington Road, Parkville, 3052 Victoria Australia.
Early Life Epigenetics Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, 3052 Victoria Australia ; Department of Paediatrics, The University of Melbourne, Children's Hospital, Flemington Road, Parkville, 3052 Victoria Australia.
Cancer and Disease Epigenetics Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, 3052 Victoria Australia ; Department of Paediatrics, The University of Melbourne, Children's Hospital, Flemington Road, Parkville, 3052 Victoria Australia.
Issue Date: 18-Mar-2015
Citation: Gigascience 2015; 4(): 11
Abstract: 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.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.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.
Internal ID Number: 25789165
URI: http://ahro.austin.org.au/austinjspui/handle/1/12694
DOI: 10.1186/s13742-015-0050-0
URL: http://www.ncbi.nlm.nih.gov/pubmed/25789165
Type: Journal Article
Subjects: Childhood leukaemia
DNA methylation
Epigenetics
NGS
SOLiD MBD-Seq
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.