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Subclonal TP53 copy number is associated with prognosis in multiple myeloma

Lookup NU author(s): Professor Graham Jackson


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© 2018 by The American Society of Hematology 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 5 .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 5 .002) or del(1p) (P 5 .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.

Publication metadata

Author(s): 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

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2018

Volume: 132

Issue: 23

Pages: 2465-2469

Online publication date: 06/12/2018

Acceptance date: 03/10/2018

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2018-06-857250


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