dc.contributor.author | Shah, V | |
dc.contributor.author | Johnson, DC | |
dc.contributor.author | Sherborne, AL | |
dc.contributor.author | Ellis, S | |
dc.contributor.author | Aldridge, FM | |
dc.contributor.author | Howard-Reeves, J | |
dc.contributor.author | Begum, F | |
dc.contributor.author | Price, A | |
dc.contributor.author | Kendall, J | |
dc.contributor.author | Chiecchio, L | |
dc.contributor.author | Savola, S | |
dc.contributor.author | Jenner, MW | |
dc.contributor.author | Drayson, MT | |
dc.contributor.author | Owen, RG | |
dc.contributor.author | Gregory, WM | |
dc.contributor.author | Morgan, GJ | |
dc.contributor.author | Davies, FE | |
dc.contributor.author | Houlston, RS | |
dc.contributor.author | Cook, G | |
dc.contributor.author | Cairns, DA | |
dc.contributor.author | Jackson, G | |
dc.contributor.author | Kaiser, MF | |
dc.contributor.author | National Cancer Research Institute Haematology Clinical Studies Group, | |
dc.date.accessioned | 2020-11-17T11:04:37Z | |
dc.date.issued | 2018-12-06 | |
dc.identifier.citation | Blood, 2018, 132 (23), pp. 2465 - 2469 | |
dc.identifier.issn | 0006-4971 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4230 | |
dc.identifier.eissn | 1528-0020 | |
dc.identifier.doi | 10.1182/blood-2018-06-857250 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 2465 - 2469 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER SOC HEMATOLOGY | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | National Cancer Research Institute Haematology Clinical Studies Group | |
dc.subject | Humans | |
dc.subject | Multiple Myeloma | |
dc.subject | Genomic Instability | |
dc.subject | Disease-Free Survival | |
dc.subject | Survival Rate | |
dc.subject | Gene Deletion | |
dc.subject | Gene Dosage | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Tumor Suppressor Protein p53 | |
dc.title | Subclonal TP53 copy number is associated with prognosis in multiple myeloma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-10-03 | |
rioxxterms.versionofrecord | 10.1182/blood-2018-06-857250 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2018-12 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Blood | |
pubs.issue | 23 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.publication-status | Published | |
pubs.volume | 132 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Genomics | |
icr.researchteam | Myeloma Group | |
dc.contributor.icrauthor | Shah, Vallari | |
dc.contributor.icrauthor | Johnson, David | |
dc.contributor.icrauthor | Houlston, Richard | |
dc.contributor.icrauthor | Kaiser, Martin | |