Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma
dc.contributor.author | Newman, AM | |
dc.contributor.author | Zaka, M | |
dc.contributor.author | Zhou, P | |
dc.contributor.author | Blain, AE | |
dc.contributor.author | Erhorn, A | |
dc.contributor.author | Barnard, A | |
dc.contributor.author | Crossland, RE | |
dc.contributor.author | Wilkinson, S | |
dc.contributor.author | Enshaei, A | |
dc.contributor.author | De Zordi, J | |
dc.contributor.author | Harding, F | |
dc.contributor.author | Taj, M | |
dc.contributor.author | Wood, KM | |
dc.contributor.author | Televantou, D | |
dc.contributor.author | Turner, Suzanne | |
dc.contributor.author | Burke, GAA | |
dc.contributor.author | Harrison, CJ | |
dc.contributor.author | Bomken, S | |
dc.contributor.author | Bacon, CM | |
dc.contributor.author | Rand, V | |
dc.date.accessioned | 2022-02-28T17:00:37Z | |
dc.date.available | 2022-02-28T17:00:37Z | |
dc.date.issued | 2020-03 | |
dc.date.submitted | 2021-03-02 | |
dc.identifier.issn | 0887-6924 | |
dc.identifier.other | s41375-021-01444-6 | |
dc.identifier.other | 1444 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/334510 | |
dc.description | Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265 | |
dc.description | Funder: Good Will Cause | |
dc.description | Funder: MRC/EPSRC Newcastle Pathology Node | |
dc.description | Funder: Newcastle upon Tyne Hospitals NHS Foundation Trust (Newcastle upon Tyne Hospitals NHS Trust); doi: https://doi.org/10.13039/501100003776 | |
dc.description | Funder: Blood Cancer UK - Senior Bennett Fellowship #12005 North East Promenaders Against Cancer (NEPAC) The Little Princess Trust JGW Patterson Foundation | |
dc.description.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. | |
dc.language | en | |
dc.publisher | Nature Publishing Group UK | |
dc.subject | Article | |
dc.subject | /631/67/69 | |
dc.subject | /692/699/1541/1990/291/1621/1915 | |
dc.subject | /45/61 | |
dc.subject | /45/22 | |
dc.subject | /45/23 | |
dc.subject | /45/77 | |
dc.subject | article | |
dc.title | Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma | |
dc.type | Article | |
dc.date.updated | 2022-02-28T17:00:37Z | |
prism.endingPage | 789 | |
prism.issueIdentifier | 3 | |
prism.publicationName | Leukemia | |
prism.startingPage | 781 | |
prism.volume | 36 | |
dc.identifier.doi | 10.17863/CAM.81928 | |
dcterms.dateAccepted | 2021-09-29 | |
rioxxterms.versionofrecord | 10.1038/s41375-021-01444-6 | |
rioxxterms.version | VoR | |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.contributor.orcid | Blain, AE [0000-0001-8045-822X] | |
dc.contributor.orcid | Turner, Suzanne [0000-0002-8439-4507] | |
dc.contributor.orcid | Burke, GAA [0000-0003-2671-9972] | |
dc.contributor.orcid | Rand, V [0000-0002-2198-8949] | |
dc.identifier.eissn | 1476-5551 |
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