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

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ICR Authors

Shah, Vallari
 Johnson, David
 Houlston, Richard
 Kaiser, Martin

Authors

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,

Document Type

Journal Article

Date

2018-12-06

Date Accepted

2018-10-03

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.

Citation

Blood, 2018, 132 (23), pp. 2465 - 2469

DOI

10.1182/blood-2018-06-857250

URI

https://repository.icr.ac.uk/handle/internal/4230

Rights

https://www.rioxx.net/licenses/all-rights-reserved

Source Title

Publisher

AMER SOC HEMATOLOGY

ISSN

0006-4971

eISSN

1528-0020

Collections

Cancer Biology
Genetics and Epidemiology

Research Team

Cancer Genomics
Myeloma Group

Notes