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Lookup NU author(s): Alex Newman, Dr Masood Zaka, Dr Peixun Zhou, Dr Amy Erhorn, Amy Barnard, Dr Rachel CrosslandORCiD, Sara Wilkinson, Karl Wood, Dr Despoina Televantou, Professor Christine Harrison, Dr Simon BomkenORCiD, Dr Christopher BaconORCiD, Dr Vikki Rand
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Background/Objectives: Current frontline therapies for paediatric B-cell non-Hodgkin lymphoma (B-NHL) are very effective, achieving >90% survival. However, for those children who relapse treatment options are limited and outcome remains poor. Little is currently known about the biology of relapsed disease and there are no markers which identify children who will relapse. We performed genome-wide copy number analysis to identify the abnormalities associated with relapsed disease. Design/Methods: We included 162 paediatric B-NHL cases in this study; 110 pre-treatment samples were obtained from the Children’s Cancer and Leukaemia Group (CCLG) Tumour bank and 52 cases were identified from the literature. Matched relapse samples were obtained for 9/18 relapse cases. High-resolution copy number data was generated using Affymetrix Cytoscan HD or Oncoscan arrays. TP53 mutations were detected using next-generation and Sanger sequencing. Univariate and multivariate analyses examined the association of abnormalities with risk of relapse, event-free and overall survival. Results: Twenty-six recurrent copy number abnormalities (CNAs) and regions of copy number neutral loss of heterozygosity (CNN-LOH) were detected by GISTIC2.0. Recurrent CNAs involved known cancer genes including MCL1, REL, BCL11A, MSH6, FBX011, CDKN2A/B, MIR17HG and TP53. TP53 mutations were identified in 46% (37/80) of cases, and 68% (25/37) had biallelic inactivation. Multivariate analysis identified TP53 biallelic inactivation as an independent prognostic factor identifying children with an increased risk of relapse (HR 3.51, 95% CI 1.22-10.14, p=0.02) and shorter event free survival (HR 3.97, 95% CI 1.04-15.07, p=0.043). Of the matched relapse samples, 6/9 (67%) cases had TP53 biallelic inactivation at relapse; 5 maintained the abnormalities from diagnosis and one acquired TP53 inactivation at relapse. Conclusion: Genome-wide analysis revealed that TP53 biallelic inactivation is associated with an increased risk of relapse and shorter event-free survival in paediatric B-NHL. Further work is essential to understand the biology and exploitation of molecular abnormalities to improve survival for relapsed B-NHL.
Author(s): Newman AM, Zaka M, Zhou P, Erhorn A, Barnard A, Crossland RE, Wilkinson S, Wood K, Televantou D, Harrison CJ, Bomken S, Bacon CM, Rand V
Publication type: Conference Proceedings (inc. Abstract)
Publication status: Published
Conference Name: 50th Congress of the International Society of Paediatric Oncology (SIOP)
Year of Conference: 2019
Pages: S46-S47
Print publication date: 21/09/2018
Online publication date: 21/09/2018
Acceptance date: 21/09/2018
ISSN: 1545-5017
Publisher: John Wiley & Sons, Inc.
URL: https://doi.org/10.1002/pbc.27455
DOI: 10.1002/pbc.27455
PubMed id: 30240102
Series Title: Pediatric Blood & Cancer
