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Lookup NU author(s): Alex Newman, Dr Peixun Zhou, Dr Masood Zaka, Professor Christine Harrison, Dr Simon BomkenORCiD, Dr Christopher BaconORCiD, Dr Vikki Rand
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Background: Over 90% of children diagnosed with Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) are cured, however outcome for adults remains poor. BL and DLBCL occur across all age groups with BL most common in children and DLBCL in adults. The age distribution of BL is bimodal, peaking in childhood and increasing steadily after age 60, whereas DLBCL significantly increases throughout adulthood. The difference in survival is, in part, due to different treatment protocols but evidence suggests additional differences in the underlying biology. Objectives: To investigate the genomic landscapes of paediatric and adult BL and DLBCL in order to identify recurrent abnormalities associated with age. Design/methods: A total of 720 cases were included in this study. 111 patient samples were obtained from the Children’s Cancer and Leukaemia Group (CCLG) Tissue Bank and high-resolution copy number data were generated using Affymetrix Cytoscan and Oncoscan arrays. Copy number data were obtained on 609 cases from eight published datasets identified via Gene Expression Omnibus (GEO) and Pubmed (NCBI). Age was available for 70% (505/720) of cases; paediatric (age 0-18 years) (n=162) and adult (age 19+) (n=343). Data was analysed in Nexus Copy Number 9.0 (BioDiscovery). Results: Overall the adult BL genome had fewer abnormalities (mean 5.5 per sample) compared to paediatric BL (29 per sample). Gain of 13q involving the MIR17HG locus was significantly more common in paediatric than adult BL (25.3% vs 8.8%, p<0.001). Gain of MIR17HG was also observed in DLBCL but was not associated with telomeric deletions. Other copy number changes more commonly affected in paediatric BL included 7q and 11q gain, and 17p loss. Gain of 7q was also frequent in adult BL and paediatric DLBCL but adults with DLBCL more commonly showed whole chromosome 7 gains. Most differences between adult and paediatric DLBCL were subtype specific (e.g. gain of chromosome 3 and 18 associated with ABC-like adult DLBCL), however, REL amplification was identified in both age groups. Conclusion: Gain of 13q31.3 involving the MIR17HG locus is the most significant region involved in copy number change and is associated with younger age in BL and DLBCL. Overall, our study shows that adult and paediatric B-cell non-Hodgkin lymphoma subtypes have similar genomic profiles, however there are clear and distinct differences which offer potential for age-associated therapeutic strategies.
Author(s): Newman AM, Zhou P, Zaka M, Harrison CJ, 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: 69-69
Print publication date: 26/09/2018
Online publication date: 19/09/2018
Acceptance date: 19/09/2018
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
