TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes

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,...

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Detalles Bibliográficos
Autores: McGraw, Kathy L., Cluzeau, Thomas, Sallman, David A., Basiorka, Ashley A., Irvine, Brittany A., Ling, Zhang, Epling-Burnette, P. K., Rollison, Dana E., Mallo, Maria del Mar|||0000-0001-7741-498X, Sokol, Lubomir, Sole, F.|||0000-0002-3251-2161, Maciejewski, Jaroslaw|||0000-0002-6837-4346, List, Alan F.
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:163246
Acceso en línea:https://ddd.uab.cat/record/163246
https://dx.doi.org/urn:doi:10.18632/oncotarget.5255
Access Level:acceso abierto
Palabra clave:MDM2
TP53
Myelodysplastic syndromes
Single nucleotide polymorphisms
Survival
Descripción
Sumario: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.

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