Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma
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Authors
Newman, AM
Zaka, M
Zhou, P
Erhorn, A
Barnard, A
Crossland, RE
Wilkinson, S
Enshaei, A
De Zordi, J
Harding, F
Taj, M
Wood, KM
Televantou, D
Harrison, CJ
Bomken, S
Bacon, CM
Publication Date
2020-03Journal Title
Leukemia
ISSN
0887-6924
Publisher
Nature Publishing Group UK
Volume
36
Issue
3
Pages
781-789
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Newman, A., Zaka, M., Zhou, P., Blain, A., Erhorn, A., Barnard, A., Crossland, R., et al. (2020). Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma. Leukemia, 36 (3), 781-789. https://doi.org/10.1038/s41375-021-01444-6
Description
Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265
Funder: Good Will Cause
Funder: MRC/EPSRC Newcastle Pathology Node
Funder: Newcastle upon Tyne Hospitals NHS Foundation Trust (Newcastle upon Tyne Hospitals NHS Trust); doi: https://doi.org/10.13039/501100003776
Funder: Blood Cancer UK - Senior Bennett Fellowship #12005 North East Promenaders Against Cancer (NEPAC) The Little Princess Trust JGW Patterson Foundation
Abstract
Abstract: Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p < 0.001, OS 78.0% vs 100%, p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols.
Keywords
Article, /631/67/69, /692/699/1541/1990/291/1621/1915, /45/61, /45/22, /45/23, /45/77, article
Identifiers
s41375-021-01444-6, 1444
External DOI: https://doi.org/10.1038/s41375-021-01444-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334510
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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