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

Publication Type:

Journal Article

Source:

Pediatric blood & cancer, Volume 55, Issue 2, p.248-53 (2010)

Keywords:

2010, Adolescent, Antineoplastic Combined Chemotherapy Protocols, Case-Control Studies, Center-Authored Paper, Child, Child, Preschool, Clinical Research Division, Female, Genetic Predisposition to Disease, Genotype, Humans, Infant, Infant, Newborn, Leukemia, Myeloid, Acute, Male, Polymorphism, Genetic, Proto-Oncogene Proteins c-mdm2, Treatment Outcome, Young Adult

Abstract:

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.