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Blood. 2018 Dec 6;132(23):2465-2469. doi: 10.1182/blood-2018-06-857250. Epub 2018 Oct 29.

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

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Division of Molecular Pathology, Institute of Cancer Research, London, United Kingdom.
Centre for Molecular Pathology, The Royal Marsden Hospital, London, United Kingdom.
Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, United Kingdom.
MRC-Holland, Amsterdam, Netherlands.
Department of Haematology, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Haematological Malignancy Diagnostic Service, St. James's University Hospital, Leeds, United Kingdom.
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, Leeds, United Kingdom.
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR.
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom; and.
Department of Haematology, University of Newcastle, Newcastle upon Tyne, United Kingdom.


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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