Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma
| Autor: | S Wilkinson, P Zhou, Christine J. Harrison, Simon Bomken, Alex E. Blain, Julian De Zordi, Chris M. Bacon, Alexander M. Newman, G. A. Amos Burke, Amir Enshaei, Mary Taj, Rachel E Crossland, Suzanne D. Turner, Despina Televantou, Amy Erhorn, Vikki Rand, Fiona Harding, Katrina M Wood, A Barnard, Masood Zaka |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Lymphoma B-Cell Adolescent Gene Dosage Gastroenterology Loss of heterozygosity Risk groups Internal medicine medicine Humans Clinical significance Stage (cooking) Child neoplasms business.industry Infant Hematology medicine.disease Lymphoma Oncology Genetic Loci Child Preschool Cohort Mutation B-Cell Non-Hodgkin Lymphoma Disease Progression Female Abnormality Tumor Suppressor Protein p53 business |
| Zdroj: | Leukemia. 36(3) |
| ISSN: | 1476-5551 |
| Popis: | 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 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 |
| Externí odkaz: |
|
Full text from SpringerLink