MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: a report from the Children's Oncology Group.

ABSTRACT:

Background

The variant polymorphism in the gene MDM2, SNP309, leads to increased level of mdm2 protein and subsequent downregulation of p53 tumor suppressor pathway. Presence of this single nucleotide polymorphism (SNP) has been associated with earlier tumorigenesis in patients with Li-Fraumeni syndrome, as well as decreased survival in patients with CLL. In addition, cells homozygous (G/G) for SNP 309 were found to have 10-fold increase resistance to topoisomerase II inhibitors in vitro.

Procedure

We genotyped children (n = 575) with de novo acute myeloid leukemia (AML) treated on three Children's Oncology Group protocols (CCG 2941/2961/AAML 03P1) for the presence of SNP309. Healthy blood donors were genotyped as control population.

Results

The variant G/G genotype w

SUBMITTER: Phillips CL 

PROVIDER: S-EPMC2915901 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature