Subclonal <i>TP53</i> copy number is associated with prognosis in multiple myeloma.
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Publication Date
2018-12Author
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 <i>TP53</i> copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal <i>TP53</i> deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; <i>P</i> = .01). Clonal, but not subclonal, <i>TP53</i> deletions were associated with clinical markers of advanced disease, specifically lower platelet counts (<i>P</i> < .001) and increased lactate dehydrogenase (<i>P</i> < .001), as well as a higher frequency of features indicative of genomic instability, del(13q) (<i>P</i> = .002) or del(1p) (<i>P</i> = .006). Biallelic <i>TP53</i> loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal <i>TP53</i> deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies.
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Licenseref URL
http://www.rioxx.net/licenses/all-rights-reservedVersion of record
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