Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma
| Autor: | Newman, AM, Zaka, M, Zhou, P, Blain, AE, Erhorn, A, Barnard, A, Crossland, RE, Wilkinson, S, Enshaei, A, De Zordi, J, Harding, F, Taj, M, Wood, KM, Televantou, D, Turner, SD, Burke, GAA, Harrison, CJ, Bomken, S, Bacon, CM, Rand, V |
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| Přispěvatelé: | Blain, AE [0000-0001-8045-822X], Turner, SD [0000-0002-8439-4507], Burke, GAA [0000-0003-2671-9972], Rand, V [0000-0002-2198-8949], Apollo - University of Cambridge Repository, Blain, Alex E [0000-0001-8045-822X], Turner, Suzanne D [0000-0002-8439-4507], Burke, GA Amos [0000-0003-2671-9972], Rand, Vikki [0000-0002-2198-8949] |
| Rok vydání: | 2020 |
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| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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