Publications Repository

Publications Repository

View Item 
  •   Home
  • ICR Divisions
  • Molecular Pathology
  • View Item
  • Home
  • ICR Divisions
  • Molecular Pathology
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Subclonal <i>TP53</i> copy number is associated with prognosis in multiple myeloma.

Thumbnail
View/Open
Accepted version (1.389Mb)
Publication Date
2018-12
ICR Author
Kaiser, Martin
Johnson, David
Houlston, Richard
Shah, Vallari
Author
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 record
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 <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.
URL
https://repository.icr.ac.uk/handle/internal/4230
Collections
  • Genetics and Epidemiology
  • Molecular Pathology
Licenseref URL
http://www.rioxx.net/licenses/all-rights-reserved
Version of record
10.1182/blood-2018-06-857250
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

Browse

All of ICR repositoryICR DivisionsIssue dateAuthorsTitlesSubjectsThis collectionIssue dateAuthorsTitlesSubjects

Statistics

Most popular itemsStatistics by countryMost popular authors
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.