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Subclonal <i>TP53</i> copy number is associated with prognosis in multiple myeloma.

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Date
2018-12
ICR Author
Kaiser, Martin
Johnson, David
Houlston, Richard
Shah, Vallari
Author
Shah, V
Johnson, DC
Sherborne, AL
Ellis, S
Aldridge, FM
Howard-Reeves, J
Begum, F
Price, A
Kendall, J
Chiecchio, L
Savola, S
Jenner, MW
Drayson, MT
Owen, RG
Gregory, WM
Morgan, GJ
Davies, FE
Houlston, RS
Cook, G
Cairns, DA
Jackson, G
Kaiser, MF
National Cancer Research Institute Haematology Clinical Studies Group
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Type
Journal Article
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Abstract
Multiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts ( P < .001) and increased lactate dehydrogenase ( P < .001), as well as a higher frequency of features indicative of genomic instability, del(13q) ( P = .002) or del(1p) ( P = .006). Biallelic TP53 loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal TP53 deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies.
URI
https://repository.icr.ac.uk/handle/internal/4230
DOI
https://doi.org/10.1182/blood-2018-06-857250
Collections
  • Genetics and Epidemiology
  • Molecular Pathology
Subject
National Cancer Research Institute Haematology Clinical Studies Group
Humans
Multiple Myeloma
Genomic Instability
Disease-Free Survival
Survival Rate
Gene Deletion
Gene Dosage
Female
Male
Tumor Suppressor Protein p53
Research team
Cancer Genomics
Myeloma Group
Language
eng
Date accepted
2018-10-03
License start date
2018-12
Citation
Blood, 2018, 132 (23), pp. 2465 - 2469

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