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Lookup NU author(s): Dr Masood Zaka, Dr Rachel CrosslandORCiD, Amy Barnard, Sara Wilkinson, Dr Simon BomkenORCiD, Dr Christopher BaconORCiD, Dr Vikki Rand
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Background: MicroRNAs play a critical role in many cancers, including lymphoma. Our knowledge, however, of microRNAs in paediatric B-cell non-Hodgkin lymphoma (B-NHL) and their relevance in disease progression is limited. To date, only miR17HG has been associated with relapsed Burkitt lymphoma (BL) in children. Objectives: Integrative analysis of global copy number and microRNA expression profiling to identify dysregulated microRNAs in paediatric relapsed B-cell non-Hodgkin lymphoma. Design/methods: Diagnostic material for 21 patients was obtained from the Children’s Cancer and Leukaemia Group (CCLG) Tissue Bank, of which nine had refractory or relapsed B-cell non-Hodgkin lymphoma (B-NHL). High-resolution copy number data and global microRNA expression data was generated using Affymetrix Cytoscan HD arrays and GeneChip miRNA 4.0 Arrays. Copy number analysis was performed using Nexus Copy Number 9.0 (BioDiscovery) and global microRNA data was background corrected and normalised using RMA in affy Bioconductor package. Differentially expressed microRNAs were identified using a linear contrast matrices model and microRNAs were considered significant with a logFC >0.5 (upregulated) and <-0.5 (downregulated) with a p-value <0.05. microRNA target genes were identified using an in-house pipeline to integrate six publically available databases. Results: An average of 29.71 (range 9-73) copy number abnormalities (CNAs) and regions of copy-number neutral loss of heterozygosity (CNN-LOH) were identified per case. The median number of CNAs/CNN-LOH was higher in the genomes of relapsed and non-relapsing cases (35 vs 26). Gain of 13q31.3-q32.1, including the MIR17HG locus, was only observed in patients who did not relapse (0% vs 42%). Deletion of the telomere of 13q (13q33.2-q34) was also not detected in relapsed cases (0% vs 42%). Differential expression identified 82 dysregulated microRNAs between patients who relapsed and those with no relapsed disease; 14 upregulated and 68 downregulated in relapse cases. Gene Set Enrichment Analysis (GSEA) identified enrichment of key pathways, including the TP53, MAPK, PI3K-AKT and B-cell Receptor signalling pathways. Conclusion: We have identified microRNAs differentially expressed in relapsed disease which regulate important pathways known to be involved in B-cell non-Hodgkin lymphoma. However, neither copy number gain of the MIR17HG locus or differential expression of the microRNA clusters were shown to be associated with relapsed disease. In summary, differentially expressed microRNAs may be important in the regulation of critical B cell/B-NHL signalling pathways.
Author(s): Zaka M, Crossland RC, Barnard A, Erhorn A, Wilkinson S, Bomken S, Bacon CM, Rand V
Publication type: Conference Proceedings (inc. Abstract)
Publication status: Published
Conference Name: Sixth International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma
Year of Conference: 2018
Pages: 80-80
Print publication date: 26/09/2018
Online publication date: 19/09/2018
Acceptance date: 19/09/2018
Date deposited: 24/04/2019
ISSN: 1365-2141
Publisher: John Wiley and Sons Ltd
URL: https://doi.org/10.1111/bjh.15536
DOI: 10.1111/bjh.15536
PubMed id: 30230525
Series Title: British Journal of Haematology
