TY - JOUR
T1 - MDM2 SNP309 genotype influences survival of metastatic but not of localized neuroblastoma
AU - Perfumo, Chiara
AU - Parodi, Stefano
AU - Mazzocco, Katia
AU - Defferrari, Raffaella
AU - Inga, Alberto
AU - Scarrà, Giovanna Bianchi
AU - Ghiorzo, Paola
AU - Haupt, Riccardo
AU - Tonini, Gian Paolo
AU - Fronza, Gilberto
PY - 2009/10
Y1 - 2009/10
N2 - Background. MDM2 is a major negative regulator of p53 function and is directly regulated by MYCN in neuroblastoma (NB) cells. MDM2 SNP309, a T-to-G substitution in the MDM2 promoter associated with higher gene expression compared to wild-type, may attenuate the p53 pathway in NB, in which p53 mutations are rare. We investigated its impact on NB development and survival in relation with major clinical and biological characteristics. Procedure. A consecutive cohort of 497 NB children, diagnosed in Italy between 1995 and 2005, and a healthy control population of 471 adults were genotyped for MDM2 SNP309. NB patients were followed up until June 30, 2008. Results. Patients and controls showed similar distribution of MDM2 SNP309 genotypes. In patients, the polymorphism was not associated with any characteristic at diagnosis. In localized stages no effect of the polymorphism on survival was evident. In stage 4 patients overall survival (OS), event free survival (EFS) and survival after relapse (SAR) were significantly poorer for TG/GG than for TT patients (P=0.008; P=0.013; P=0.046, respectively). In this group, such an effect was more evident in patients with MYCN amplification (OS: P
AB - Background. MDM2 is a major negative regulator of p53 function and is directly regulated by MYCN in neuroblastoma (NB) cells. MDM2 SNP309, a T-to-G substitution in the MDM2 promoter associated with higher gene expression compared to wild-type, may attenuate the p53 pathway in NB, in which p53 mutations are rare. We investigated its impact on NB development and survival in relation with major clinical and biological characteristics. Procedure. A consecutive cohort of 497 NB children, diagnosed in Italy between 1995 and 2005, and a healthy control population of 471 adults were genotyped for MDM2 SNP309. NB patients were followed up until June 30, 2008. Results. Patients and controls showed similar distribution of MDM2 SNP309 genotypes. In patients, the polymorphism was not associated with any characteristic at diagnosis. In localized stages no effect of the polymorphism on survival was evident. In stage 4 patients overall survival (OS), event free survival (EFS) and survival after relapse (SAR) were significantly poorer for TG/GG than for TT patients (P=0.008; P=0.013; P=0.046, respectively). In this group, such an effect was more evident in patients with MYCN amplification (OS: P
KW - MDM2
KW - Neuroblastoma
KW - Polymorphism
KW - Progression
KW - Survival
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U2 - 10.1002/pbc.22132
DO - 10.1002/pbc.22132
M3 - Article
C2 - 19526525
AN - SCOPUS:69849106415
VL - 53
SP - 576
EP - 583
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
SN - 1545-5009
IS - 4
ER -