TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes
McGraw, Kathy L. (Moffitt Cancer Center and Research Institute (Florida, Estats Units d'Amèrica))
Cluzeau, Thomas (Centre Hospitalier Universitaire de Nice (França))
Sallman, David A. (Moffitt Cancer Center and Research Institute (Florida, Estats Units d'Amèrica))
Basiorka, Ashley A. (University of South Florida (Estats Units d'Amèrica))
Irvine, Brittany A. (Moffitt Cancer Center and Research Institute (Florida, Estats Units d'Amèrica))
Ling, Zhang (Moffitt Cancer Center and Research Institute (Florida, Estats Units d'Amèrica))
Epling-Burnette, P. K. (Moffitt Cancer Center and Research Institute (Florida, Estats Units d'Amèrica))
Rollison, Dana E. (Moffitt Cancer Center and Research Institute (Florida, Estats Units d'Amèrica))
Mallo, Maria del Mar (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Sokol, Lubomir (Moffitt Cancer Center and Research Institute (Florida, Estats Units d'Amèrica))
Sole, F (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Maciejewski, Jaroslaw (Taussig Cancer Institute (Cleveland, Estats Units d'Amèrica))
List, Alan F. (Moffitt Cancer Center and Research Institute (Florida, Estats Units d'Amèrica))

Date:	2015
Abstract:	Abstract:P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to -2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0. 02) and progression-free survival (PFS) (p = 0. 02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome.
Grants:	Ministerio de Economía y Competitividad PI/11/02010 Ministerio de Economía y Competitividad PI/14/00013
Note:	Altres ajuts: National Cancer Institute/National Institute of Health (5 R01CA131076-04); Molecular Genomics Facility (P30-CA076292); Sociedad Española Hematología y Hemoterapia (2014 SGR225); Fundació Internacional Josep Carreras i Celgene Spain. RTICC/RD12/0036/0044
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	MDM2 ; TP53 ; Myelodysplastic syndromes ; Single nucleotide polymorphisms ; Survival
Published in:	Oncotarget, Vol. 6 Núm. 33 (october 2015) , ISSN 1949-2553

DOI: 10.18632/oncotarget.5255
PMID: 26416416

9 p, 1.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles