Document Type

Article

Publication Date

2015

Keywords

TP53, MDM2, myelodysplastic syndromes, single nucleotide polymorphisms, survival

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.

Digital Object Identifier (DOI)

https://doi.org/10.18632/oncotarget.5255

Rights Information

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Citation / Publisher Attribution

Oncotarget, v. 6, issue 33, p. 34437-34445

Was this content written or created while at USF?

Yes

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