Subclonal TP53 copy number is associated with prognosis in multiple myeloma.

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Date
2018-12-06Author
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,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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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
Publisher
AMER SOC HEMATOLOGY